Seattle Cancer Care Alliance at
ASCO
June 4-8, 2021
Virtual

From June 4-8, the American Society of Clinical Oncology  (ASCO) will host its annual meeting, showcasing important scientific insights from around the world. At this year's virtual meeting, world-class physicians and researchers from Seattle Cancer Care Alliance (SCCA) and our partner organizations will be presenting their pioneering research. 

Schedule and abstracts

Our leading physician researchers will have their oral presentations, poster discussions and poster sessions available on demand through the virtual conference.

Filter conference by
Selected tags
Friday, June 4th
6:00 AM
Oral
Breast cancer screening for carriers of ATM, CHEK2, and PALB2 pathogenic variants: A comparative modeling analysis.

 Inherited pathogenic variants in ATM, CHEK2, and PALB2 confer moderate to high risks of breast cancer. The optimal approach to screening in these women has not been established.

Speaker
Kathryn P. Lowry, MD
Disease/Specialty
Breast cancer, Screening/prevention

Research Funding: Breast Cancer Research Foundation, U.S. National Institutes of Health

Background:Inherited pathogenic variants in ATM, CHEK2, and PALB2 confer moderate to high risks of breast cancer. The optimal approach to screening in these women has not been established.

Methods:We used two simulation models from the Cancer Intervention and Surveillance Modeling Network (CISNET) and data from the Cancer Risk Estimates Related to Susceptibility consortium (CARRIERS) to project lifetime breast cancer incidence and mortality in ATM, CHEK2, and PALB2 carriers. We simulated screening with annual mammography from ages 40-74 alone and with annual magnetic resonance imaging (MRI) starting at ages 40, 35, 30, and 25. Joint and separate mammography and MRI screening performance was based on published literature. Lifetime outcomes per 1,000 women were reported as means and ranges across both models.

Results:Estimated risk of breast cancer by age 80 was 22% (21-23%) for ATM, 28% (26-30%) for CHEK2, and 40% (38-42%) for PALB2. Screening with MRI and mammography reduced breast cancer mortality by 52-60% across variants (Table). Compared to no screening, starting MRI at age 30 increased life years (LY)/1000 women by 501 (478-523) in ATM, 620 (587-652) in CHEK2, and 1,025 (998-1,051) in PALB2. Starting MRI at age 25 versus 30 gained 9-12 LY/1000 women with 517-518 additional false positive screens and 197-198 benign biopsies.

Conclusions:For women with ATM, CHEK2, and PALB2 pathogenic variants, breast cancer screening with MRI and mammography halves breast cancer mortality. These mortality benefits are similar to those for MRI screening for BRCA1/2 mutation carriers and should inform practice guidelines.

Poster
Phase I study of adoptive immunotherapy for advanced MUC1* positive breast cancer with autologous T cells engineered to express a chimeric antigen receptor, huMNC2-CAR44 specific for a cleaved form of MUC1 (MUC1*).

Chimeric antigen receptor (CAR) T cell therapy targeting CD19 results in marked tumor regression for patients with CD19+ malignancies. It would be ideal to extend the success of CAR-T cell therapy to epithelial cancers. MUC1* is a post-translationally modified/cleaved form of mucin 1 (MUC1) that is frequently expressed on breast tumors, functions as a growth factor receptor, and a promising antigen for CAR-T cell therapy. Minerva Biotechnologies developed a CAR (huMNC2-CAR44) which recognizes MUC1* and does not bind to full-length or MUC1* negative cells. huMNC2-CAR44 product consists of autologous T cells transduced with a lentiviral vector encoding humanized MNC2-scFv (MUC1* targeting head), sequences from CD8 ?? leader, hinge and transmembrane domains, 4-1BB and CD3ζ domains.

Speaker
Jennifer M. Specht, MD
Disease/Specialty
Immunotherapy, Personalized medicine

Research Funding: Minerva Biotechnologies, Other Foundation

Background: Chimeric antigen receptor (CAR) T cell therapy targeting CD19 results in marked tumor regression for patients with CD19+ malignancies. It would be ideal to extend the success of CAR-T cell therapy to epithelial cancers. MUC1* is a post-translationally modified/cleaved form of mucin 1 (MUC1) that is frequently expressed on breast tumors, functions as a growth factor receptor, and a promising antigen for CAR-T cell therapy. Minerva Biotechnologies developed a CAR (huMNC2-CAR44) which recognizes MUC1* and does not bind to full-length or MUC1* negative cells. huMNC2-CAR44 product consists of autologous T cells transduced with a lentiviral vector encoding humanized MNC2-scFv (MUC1* targeting head), sequences from CD8 ?? leader, hinge and transmembrane domains, 4-1BB and CD3ζ domains.

Methods: NCT04020575 is a phase I study evaluating the safety of adoptively transferred autologous T cells genetically modified to express huMNC2-CAR44 in patients with metastatic MUC1* positive breast cancer. After screening, leukapheresis is performed, CD8+ and CD4+ T cells are selected, transduced with huMNC2-CAR44, expanded, and antigen stimulated in vitro. Lymphodepletion with cyclophosphamide and fludarabine is followed by infusion of huMNC2-CAR44 CAR-T cells in escalating doses (3.3 x 105 CAR+ T cells/kg – 1 x 107 CAR+ T cells/kg). Key inclusion criteria include metastatic breast cancer of known ER, PR and HER2 status, MUC1* membrane expression > or = 30% with 2+ staining by IHC, measurable or evaluable disease, receipt of standard systemic therapies known to confer benefit, age > 18, informed consent, adequate organ function, and KPS > or = 60%. Patients with active autoimmune disease, uncontrolled infection, anticipated survival < 3 months, and/or untreated CNS metastases are not eligible. The primary objective is to identify the maximum tolerated (MTD) dose of huMNC2-CAR44 T cells by CTCAE v5 and Lee criteria. Secondary objectives include persistence and phenotype of adoptively transferred huMNC2-CAR44 T cells and preliminary antitumor activity. Exploratory objectives include trafficking of huMNC2-CAR44 T cells to tumor sites, effector function of huMNC2-CAR44 T cells in vivo, association between tumor MUC1* expression and huMNC2-CAR44 T cell persistence and response, change in tumor immune microenvironment by multiplex IHC in pre- and post-treatment tumor biopsies. Dose escalation is completed using a "3+3" design. Once the MTD has been determined, up to 15 more patients will be enrolled in each of 3 expansion cohorts (Luminal, HER2 positive, and TNBC) to inform future huMNC2-CAR44 T cell trials. Study is open to screening and enrollment in dose escalation. Up to 69 patients may be enrolled in dose escalation and expansion phases. Clinical trial information: NCT04020575

Poster discussion
PrE0807: A phase Ib feasibility trial of neoadjuvant nivolumab (N) without or with lirilumab (L) in cisplatin-ineligible patients (pts) with muscle-invasive bladder cancer (MIBC).

Neoadjuvant cisplatin-based chemotherapy (CT) prior to radical cystectomy (RC) improves overall survival (OS) in MIBC, but about half of pts are cisplatin-unfit or refuse it. Neoadjuvant immune checkpoint inhibitors can induce high pathologic complete response rate (ypT0N0). The combination of anti-PD-1 (N) and anti-KIR (L) is hypothesized to be safe and have significant activity based on the complementary and possibly synergistic roles in regulating adaptive and innate immune response in MIBC.

Speaker
Petros Grivas, MD, PhD
Disease/Specialty
Bladder cancer, Personalized medicine

Research Funding: Bristol Myers Squibb

Background: Neoadjuvant cisplatin-based chemotherapy (CT) prior to radical cystectomy (RC) improves overall survival (OS) in MIBC, but about half of pts are cisplatin-unfit or refuse it. Neoadjuvant immune checkpoint inhibitors can induce high pathologic complete response rate (ypT0N0). The combination of anti-PD-1 (N) and anti-KIR (L) is hypothesized to be safe and have significant activity based on the complementary and possibly synergistic roles in regulating adaptive and innate immune response in MIBC.

Methods: This is a phase Ib multi-institutional trial in pts with localized MIBC treated with 2 neoadjuvant doses (4 weeks apart) of N alone (480 mg) in cohort 1 or N (480 mg) + L (240 mg) in cohort 2 prior to RC without adjuvant therapy (NCT03532451). Cohorts were enrolled sequentially and were not randomized. Key eligibility criteria included stage cT2-4aN0-1M0, ≥20% tumor content at TURBT and cisplatin-ineligibility (Galsky criteria) or refusal. Primary endpoint was safety manifested as rate of ≥G3 treatment related adverse events (TRAE) assessed in each cohort with CTCAE v5.0. Key secondary endpoints included the % of pts who had RC > 6 weeks after last neoadjuvant dose due to TRAE, CD8+ T cell density at RC, ypT0N0 and < ypT2N0 rates, CD8+ T cell density change between TURBT and RC, recurrence-free survival (RFS) and biomarkers in tumor tissue, blood and urine.

Results: Among 43 pts enrolled (13 cohort 1, 30 cohort 2), median age was 75 (51-89), 67% were men, all had PS ECOG 0-1. Pts were cisplatin-ineligible due to impaired renal function (47%) and hearing loss (37%), while 14 % refused cisplatin. At baseline, 37 pts had cT2 stage, 2 had cN1 and 3 cNx. In cohort 1 and 2, 13 and 29 pts, respectively, completed intended neoadjuvant treatment, and 41/43 underwent RC (12/13 cohort 1, 29/30 cohort 2). One pt progressed to metastatic disease prior to RC (cohort 1) and 1 withdrew consent prior to being treated (cohort 2). Additionally, 1 patient was found to have cervical cancer at RC. Median time from last neoadjuvant dose to RC was 27 (95%CI: 24-29) days. There was no RC delayed > 6 weeks from treatment completion due to TRAE. G3 TRAEs occurred in 0% with N and 6.7% (90%CI 1.2-19.5%) in N+L (1: arthralgia, 1: gout, 2: hip pain) that all resolved. No G4/5 TRAEs occurred. Of 40 pts with MIBC and RC, ypT0N0 rates for N and N+L were 8% and 18%, while < ypT2N0 rates were 17% and 29%, respectively. Data on RFS and OS, and biomarker data were not yet mature.

Conclusions: Neoadjuvant N alone and N+L combination prior to RC were safe, feasible and well tolerated in cisplatin-ineligible pts with MIBC, but ypT0N0 rates were unexpectedly low, especially with N alone. Two phase 3 trials (NCT03661320; NCT04209114) are evaluating the peri-operative role of N + chemotherapy +/- Linrodostat in cisplatin-fit and N +/- Bempeg in cisplatin unfit patients and are also assessing biomarkers. Clinical trial information: NCT03532451

Poster discussion
Avelumab first-line (1L) maintenance plus best supportive care (BSC) versus BSC alone for advanced urothelial carcinoma (UC): Analysis of time to end of next-line therapy in JAVELIN Bladder 100.

Avelumab 1L maintenance is approved in various countries for patients (pts) with advanced UC that has not progressed with 1L platinum-based chemotherapy based on significantly prolonged overall survival (OS) seen with avelumab + BSC vs BSC alone in the phase 3 JAVELIN Bladder 100 trial. OS was prolonged despite the more frequent use of subsequent anticancer therapy in the BSC alone arm (42.3% in the avelumab + BSC arm vs 61.7% in the BSC alone arm), most commonly with immune checkpoint inhibitors (6.3% vs 43.7%, respectively). To further characterize the efficacy benefits of avelumab 1L maintenance, we report a post hoc analysis of the time to end of next-line therapy (for any reason) in the randomized trial population.

Speaker
Petros Grivas, MD, PhD
Disease/Specialty
Bladder cancer, Personalized medicine

Research Funding: Funded by Pfizer as part of an alliance between Merck KGaA, Darmstadt, Germany and Pfizer

Background: Avelumab 1L maintenance is approved in various countries for patients (pts) with advanced UC that has not progressed with 1L platinum-based chemotherapy based on significantly prolonged overall survival (OS) seen with avelumab + BSC vs BSC alone in the phase 3 JAVELIN Bladder 100 trial. OS was prolonged despite the more frequent use of subsequent anticancer therapy in the BSC alone arm (42.3% in the avelumab + BSC arm vs 61.7% in the BSC alone arm), most commonly with immune checkpoint inhibitors (6.3% vs 43.7%, respectively). To further characterize the efficacy benefits of avelumab 1L maintenance, we report a post hoc analysis of the time to end of next-line therapy (for any reason) in the randomized trial population.

Methods: In JAVELIN Bladder 100 (NCT02603432), eligible pts had unresectable locally advanced or metastatic UC without disease progression with 4 to 6 cycles of 1L gemcitabine + either cisplatin or carboplatin. The primary endpoint was OS from randomization, assessed in 2 populations: all pts and pts with PD-L1+ tumors (Ventana SP263). In this exploratory analysis, time from randomization until end of next-line treatment received after first progression (due to death or discontinuation) was assessed.

Results: A total of 700 pts were randomized 1:1 to avelumab 1L maintenance + BSC or BSC alone. Among all randomized pts, time to end of next-line therapy was prolonged in the avelumab + BSC arm vs the BSC alone arm (Table). Time to end of next-line therapy was also longer in the avelumab + BSC arm vs the BSC alone arm in pts with PD-L1+ tumors (n = 358) or PD-L1− tumors (n = 270).

Conclusions: Pts who received avelumab 1L maintenance + BSC had prolonged time to end of next-line treatment compared with those who received BSC alone, irrespective of PD-L1 status. These data provide further evidence of the efficacy of a maintenance approach with avelumab in pts with advanced UC that has not progressed with 1L platinum-based chemotherapy. Clinical trial information: NCT02603432.

Poster
The fluciclovine (FACBC) PET/CT site-directed therapy of oligometastatic prostate cancer (Flu-BLAST-PC) trial.

Patients with biochemical recurrence (BCR) after local definitive therapy for prostate cancer (PC) represent the largest group of patients alive with PC in the United States. For patients with BCR after both radical prostatectomy and radiation, no further definitive treatment options currently exist as standard of care. FACBC PET/CT is a next-generation imaging modality approved in 2016 for suspected PC recurrence based on elevated PSA levels following prior treatment. FACBC PET/CT allows for earlier detection at lower PSA levels of oligometastatic PC in patients who would otherwise be considered as having micro-metastatic disease. FACBC PET/CT may provide potential targets for site-directed therapy; however, it is unknown whether this approach leads to improvement in clinically relevant outcomes.

Speaker
Risa L. Wong, MD
Disease/Specialty
Prostate cancer

Research Funding: Institute for Prostate Cancer Research, Pharmaceutical/Biotech Company

Background: Patients with biochemical recurrence (BCR) after local definitive therapy for prostate cancer (PC) represent the largest group of patients alive with PC in the United States. For patients with BCR after both radical prostatectomy and radiation, no further definitive treatment options currently exist as standard of care. FACBC PET/CT is a next-generation imaging modality approved in 2016 for suspected PC recurrence based on elevated PSA levels following prior treatment. FACBC PET/CT allows for earlier detection at lower PSA levels of oligometastatic PC in patients who would otherwise be considered as having micro-metastatic disease. FACBC PET/CT may provide potential targets for site-directed therapy; however, it is unknown whether this approach leads to improvement in clinically relevant outcomes.

Methods: Flu-BLAST-PC (ClinicalTrials.gov Identifier: NCT0417543) is a prospective, interventional study enrolling men with PC and BCR who have previously undergone both radical prostatectomy and adjuvant or salvage radiation to the prostatic fossa, with PSA ≥0.5 to < 10 ng/mL, PSA doubling time > 3 to < 18 months, and no radiographically detectable metastases by conventional CT and bone scan imaging. Enrolled patients undergo FACBC PET/CT imaging, and those with no PC metastases detected (Group 1) undergo observation with repeat FACBC PET/CT performed at PSA thresholds of > 2 and > 5 ng/mL, with eligibility for the trial ending at PSA ≥10 ng/mL if FACBC PET/CT remains negative. Those with 1-3 PC regions (defined as radiation fields) detected on FACBC PET/CT (Group 2) undergo site-directed therapy with surgery (e.g. lymphadenectomy) and/or radiation, as well as six months of systemic treatment with androgen deprivation therapy (ADT) and abiraterone acetate with prednisone. Patients with ≥4 PC regions detected on FACBC PET/CT (Group 3) undergo six months of ADT and abiraterone acetate with prednisone without any site-directed therapy. Patients initially in Group 1 who subsequently have PC metastases detected on repeat FACBC PET/CT imaging per protocol join Group 2 or Group 3 based on the number of PC regions involved. Given the long anticipated survival of patients with PC and BCR, the primary endpoint of the study is undetectable PSA ( < 0.2 ng/mL) rate in Group 2 at two years beyond study treatment, with secondary endpoints including the same outcome measure for Group 3, undetectable PSA rate two years after testosterone recovery from ADT in Groups 2 and 3, time to re-initiation of ADT, overall survival, and safety and tolerability. Assuming a null hypothesis of 15% undetectable PSA rate for patients with BCR two years after completing ADT and alternative hypothesis of improvement to 40% in Group 2, planned enrollment is 65 patients in Group 2. This will provide 90% power at the two-sided significance level of 0.05. Five patients have enrolled to date. Clinical trial information: NCT0417543.

Poster
Clinical accuracy of information extracted from prostate needle biopsy pathology reports using Natural language processing.

Patients with prostate cancer are diagnosed through a prostate needle biopsy (PNB). Information contained in PNB pathology reports is critical for informing clinical risk stratification and treatment; however, patient comprehension of PNB pathology reports is low, and formats vary widely by institution. Natural language processing (NLP) models trained to automatically extract key information from unstructured PNB pathology reports could be used to generate personalized educational materials for patients in a scalable fashion and expedite the process of collecting registry data or screening patients for clinical trials. As proof of concept, we trained and tested four NLP models for accuracy of information extraction.

Speaker
Risa L. Wong, MD
Disease/Specialty
Prostate cancer, Natural language processing

Research Funding: American Cancer Society, Fred Hutchinson Cancer Research Center, University of Washington

Background: Patients with prostate cancer are diagnosed through a prostate needle biopsy (PNB). Information contained in PNB pathology reports is critical for informing clinical risk stratification and treatment; however, patient comprehension of PNB pathology reports is low, and formats vary widely by institution. Natural language processing (NLP) models trained to automatically extract key information from unstructured PNB pathology reports could be used to generate personalized educational materials for patients in a scalable fashion and expedite the process of collecting registry data or screening patients for clinical trials. As proof of concept, we trained and tested four NLP models for accuracy of information extraction.

Methods: Using 403 positive PNB pathology reports from over 80 institutions, we converted portable document formats (PDFs) into text using the Tesseract optical character recognition (OCR) engine, removed protected health information using the Philter open-source tool, cleaned the text with rule-based methods, and annotated clinically relevant attributes as well as structural attributes relevant to information extraction using the Brat Rapid Annotation Tool. Text pre-processing for classification and extraction was done using Scispacy and rule-based methods. Using a 75:25 train:test split (N = 302, 101), we tested conditional random field (CRF), support vector machine (SVM), bidirectional long-short term memory network (Bi-LSTM), and Bi-LSTM-CRF models, reserving 46 training reports as a validation subset for the latter two models. Model-extracted variables were compared with values manually obtained from the unprocessed PDF reports for clinical accuracy.

Results: Clinical accuracy of model-extracted variables is reported in the Table. CRF was the highest performing model, with accuracies of 97% for Gleason grade, 82% for percentage of positive cores ( < 50% vs. ≥50%), 90% for perineural or lymphovascular invasion, and 100% for presence of non-acinar carcinoma histology. On manual review of inaccurate results, model performance was limited by PDF image quality, errors in OCR processing of tables or columns, and practice variability in reporting number of biopsy cores.

Conclusions: Our results demonstrate successful proof of concept for the use of NLP models in accurately extracting information from PNB pathology reports, though further optimization is needed before use in clinical practice.

Poster
Concordance of DNA damage repair (DDR) gene mutations in paired primary and metastatic prostate cancer (PC) samples.

Mutations in DDR genes represent actionable alterations that can be used to guide precision medicine strategies in men with advanced PC. However, acquisition of contemporary tissue samples for advanced molecular testing can be a barrier to deploying precision medicine approaches. We hypothesized that most DDR alterations represent early truncal events in PC and that archival primary tissue would faithfully reflect mutations found in cell-free circulating tumor (ctDNA) and/or metastatic tissue.

Speaker
Michael T. Schweizer, MD
Disease/Specialty
Prostate cancer, Personalized medicine

Research Funding: None

Background: Mutations in DDR genes represent actionable alterations that can be used to guide precision medicine strategies in men with advanced PC. However, acquisition of contemporary tissue samples for advanced molecular testing can be a barrier to deploying precision medicine approaches. We hypothesized that most DDR alterations represent early truncal events in PC and that archival primary tissue would faithfully reflect mutations found in cell-free circulating tumor (ctDNA) and/or metastatic tissue.

Methods: Patients were included in this study if a DDR pathway mutation was detected in metastatic tissue or ctDNA and primary tissue sequencing was available for comparison. Sequencing data from three cohorts were analyzed: 1) FoundationOne, 2) University of Washington (UW-OncoPlex or SU2C/PCF International Dream Team sequencing pipelines) and 3) University of Washington rapid autopsy series. Only pathogenic somatic mutations were included and we required ≥30 days between primary tumor tissue and ctDNA/tumor tissue acquisition. Clonal hematopoiesis of indeterminant potential (CHIP) and germline events were adjudicated by an expert molecular pathologist and excluded. Variants detected only in plasma were considered likely to be CHIP or low subclones if the variant fraction was <1% and/or >5-fold less than the estimate tumor content in plasma.

Results: Paired primary and ctDNA/metastatic samples were sequenced from 72 individuals with known DDR alterations. After excluding ctDNA cases where only CHIP (N=13) and/or germline events (N=7) were observed, 51 subjects remained and were included in the final analysis. The median time from acquisition of primary tissue to acquisition of ctDNA or tumor tissue was 52 mos (range: 1 – 193 mos). Concordance in DDR genes across samples was 86% (95% CI: 74-93%). Rates of concordance between metastatic-primary and ctDNA-primary pairs were similar when CHIP cases were excluded (87% and 85%, respectively). BRCA2 reversion mutations associated with resistance to PARP inhibitors and platinum chemotherapy were detected in ctDNA from two subjects.

Conclusions: These data provide evidence that primary prostate tissue accurately reflect the mutational status of actionable DDR genes in men with metastatic PC, supporting the hypothesis that DDR alterations are early truncal events. After excluding likely CHIP events, ctDNA profiling accurately captured these truncal DDR mutations, while also detecting reversion alterations that may suggest potential resistance mechanisms.

Poster
CD19 CAR T-cell product type independently impacts CRS and ICANS severity in patients with aggressive NHL.

CD19-targeted chimeric antigen receptor-engineered (CD19 CAR) T cells achieve high response rates in patients (pts) with relapsed or refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (NHL), but are limited by cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Pivotal trial data suggested distinct toxicity risks across CD19 CAR T-cell products, but differences in pt and disease characteristics may have confounded these observations. Thus, we assessed the independent impact of 3 CD19 CAR T-cell products (axicabtagene ciloleucel[axicel], tisagenlecleucel [tisacel], and JCAR014) on CRS and ICANS severity in 136 pts with R/R aggressive NHL.

Speaker
Jordan Gauthier, MD, MSc
Disease/Specialty
Hematology

Research Funding: U.S. National Institutes of Health

Background: CD19-targeted chimeric antigen receptor-engineered (CD19 CAR) T cells achieve high response rates in patients (pts) with relapsed or refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (NHL), but are limited by cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Pivotal trial data suggested distinct toxicity risks across CD19 CAR T-cell products, but differences in pt and disease characteristics may have confounded these observations. Thus, we assessed the independent impact of 3 CD19 CAR T-cell products (axicabtagene ciloleucel[axicel], tisagenlecleucel [tisacel], and JCAR014) on CRS and ICANS severity in 136 pts with R/R aggressive NHL.

Methods: We retrospectively analyzed aggressive NHL pts treated at our institutions with cyclophosphamide and fludarabine lymphodepletion (LD) followed by CD19 CAR T-cell therapy. Axicel and tisacel pts were treated off trial using commercial products. JCAR014 (defined-composition 4-1BB-costimulated CD19 CAR T cells) was administered in all pts at the dose of 2x106/kg on a phase I/II clinical trial (NCT01865617). CRS and ICANS were graded according to the ASTCT criteria and CTCAE 4.03, respectively. We used multivariable proportional odds logistic regression to model CRS and ICANS grade.

Results: The CAR T-cell product was axicel, tisacel, or JCAR014 in 50%, 28%, and 22% of pts, respectively. Compared to axicel pts, we observed higher preLD LDH levels in tisacel and JCAR014 pts, and lower preLD albumin with tisacel (p < 0.001) with comparable age and hematopoietic cell transplantation comorbidity (HCT-CI) indexes across CAR T-cell products. Higher day-28 overall response rate by Lugano criteria was observed after axicel (71%) compared to tisacel (56%) and JCAR014 (53%). Adjusting for age, HCT-CI, preLD LDH, preLD albumin, CAR T-cell product type was associated with CRS severity (tisacel versus [vs] axicel, OR = 0.45, p = 0.05; JCAR014 vs axicel, OR = 0.29, p = 0.005;). Age had limited or no impact on CRS severity (OR 95%CI, 0.97-1.02), while the effect of HCT-CI was undetermined (OR 95%CI, 0.85-1.27). In a multivariable model including the same covariates as above, CAR T-cell product type (tisacel vs axicel, OR =.14, p <.001; JCAR014 vs axicel, OR = 0.31, p = 0.009), preLD LDH (OR, 3.96 per log10 increase; p = 0.04) and age (OR per 10-year increase, 1.32; p =.06) were associated with ICANS severity. Interaction effect testing suggested effect modification of age by the CAR T-cell product type (tisacel/JCAR014 versus axicel, p = 0.06); using a multivariable model including this interaction term, the predicted probabilities of grade ≥3 ICANS in a 70 year-old after axicel, tisacel, and JCAR014 were 40%, 6%, and 8%, respectively.

Conclusions: CAR T-cell product type independently impacts CRS and ICANS severity in NHL pts. Our findings provide key insights to guide patient and CAR T-cell product selection.

Poster discussion
Demographics, outcomes, and risk factors for patients (Pts) with sarcoma and COVID-19: A multi-institutional cohort analysis.

Sarcoma pts often receive aggressive, highly immunosuppressive therapy and may be at high risk for severe COVID-19. Demographics, outcomes and risk factors for pts with sarcoma and COVID-19 are unknown. We aimed to describe the course of COVID-19 in sarcoma pts and to identify factors associated with adverse outcomes.

Speaker
Michael J. Wagner, MD
Disease/Specialty
Sarcoma, COVID-19

Research Funding: U.S. National Institutes of Health

Background: Sarcoma pts often receive aggressive, highly immunosuppressive therapy and may be at high risk for severe COVID-19. Demographics, outcomes and risk factors for pts with sarcoma and COVID-19 are unknown. We aimed to describe the course of COVID-19 in sarcoma pts and to identify factors associated with adverse outcomes.

Methods: The COVID-19 and Cancer Consortium (NCT04354701) is an international registry of pts with cancer and COVID-19. Adult pts (≥18 years old) with a diagnosis of sarcoma and laboratory confirmed SARS-CoV-2 were included from 50 participating institutions. Data including demographics, sarcoma diagnosis and treatment, and course of COVID-19 infection were analyzed. Primary outcome was the composite rate of hospitalization or death at 30 days from COVID-19 diagnosis. Secondary outcomes were 30 day all-cause mortality, rate of hospitalization, O2 need, and ICU admission. Descriptive statistics and univariate Fisher tests are reported.

Results: From March 17, 2020 to February 6, 2021, N=204 pts were included. Median follow up was 42 days. Median age was 58 years (IQR 43-67). 97 (48%) were male. 30 (15%) had ECOG performance status ≥2. 104 (51%) received cancer treatment, including surgery or radiation, within 3 months of COVID-19 diagnosis. 153 (75%) had active cancer, of whom 34 (22%) had lung metastases. 100 (49%) pts met the composite primary endpoint; 96 (47%) were hospitalized and 18 (9%) died within 30 days from COVID-19 diagnosis. 64 (31%) required oxygen, and 16 (8%) required ICU admission. Primary endpoint rates were similar for pts who received cytotoxic chemotherapy (38/58, 66%) or targeted therapy (16/28, 57%). Pts with higher rates of the primary endpoint included patients ≥60 years old (59% vs 40%, OR 2.04, 95% CI 1.12-3.74, p=0.016), pts with ECOG PS ≥2 vs 0-1 (90% vs 41%, OR 12.2, 95% CI 3.44-66.8, p<0.001), pts receiving any systemic therapy within 3 months of COVID-19 diagnosis (62% vs 39%, OR 2.65, 95% CI 1.43-4.97, p=0.001), and pts with lung metastases (68% vs 42%, OR 2.77, 95% CI 1.19-6.79, p=0.013). Primary endpoint rates were similar across sarcoma subtypes (Table).

Conclusions: This is the largest cohort study of pts with sarcoma and COVID-19 to date. Sarcoma pts have high rates of complications from COVID-19. Older patients, those with poor performance status, those recently receiving systemic cancer therapy, and those with lung metastases appear to have worse outcomes.

Poster discussion
Avelumab in patients with previously treated Merkel cell carcinoma (JAVELIN Merkel 200): Updated overall survival data after more than five years of follow up.

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer. Although MCC is considered chemosensitive, patients typically have limited survival benefit with chemotherapy. Before the approval of immune checkpoint inhibitors, patients with metastatic MCC (mMCC) had a poor prognosis, with a historical 5-year overall survival (OS) rate of approximately 14%. Avelumab (anti–PD-L1) became the first approved treatment for patients with mMCC, based on efficacy and safety data observed in the phase 2 JAVELIN Merkel 200 trial (NCT02155647), in which patients with mMCC received avelumab monotherapy. We report the long-term OS data from the cohort of patients with mMCC whose disease had progressed after ≥1 prior line of chemotherapy.

Speaker
Paul Nghiem, MD, PhD
Disease/Specialty
Skin cancer, Metastatic/advanced

Research Funding: Funded by Merck KGaA, Darmstadt, Germany as part of an alliance between Merck KGaA and Pfizer

Background: Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer. Although MCC is considered chemosensitive, patients typically have limited survival benefit with chemotherapy. Before the approval of immune checkpoint inhibitors, patients with metastatic MCC (mMCC) had a poor prognosis, with a historical 5-year overall survival (OS) rate of approximately 14%. Avelumab (anti–PD-L1) became the first approved treatment for patients with mMCC, based on efficacy and safety data observed in the phase 2 JAVELIN Merkel 200 trial (NCT02155647), in which patients with mMCC received avelumab monotherapy. We report the long-term OS data from the cohort of patients with mMCC whose disease had progressed after ≥1 prior line of chemotherapy.

Methods: Eligible patients had histologically confirmed, measurable (per RECIST 1.1) stage IV MCC. Patients received avelumab 10 mg/kg by intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxicity, or withdrawal. Long-term OS was analyzed; updated data for other efficacy endpoints, including response and progression-free survival, were not obtained.

Results: A total of 88 patients were enrolled and received avelumab treatment. As of September 25, 2020 (data cutoff), median follow-up was 65.1 months (range, 60.8-74.1 months). Median OS was 12.6 months (95% CI, 7.5-17.1 months); the 48- and 60-month OS rates were 30% (95% CI, 20%-40%) and 26% (95% CI, 17%-36%), respectively. At data cutoff, treatment was ongoing in 1 patient (1.1%) and an additional patient (1.1%) had reinitiated avelumab after previously discontinuing treatment. Reasons for treatment discontinuation were disease progression (n = 45 [51.1%]), adverse event (AE; n = 11 [12.5%]), death (n = 10 [11.4%]), withdrawal of consent (n = 9 [10.2%]), loss to follow-up (n = 1 [1.1%]), protocol noncompliance (n = 1 [1.1%]), and other reason (n = 10 [11.4%]). At data cutoff, 19 patients (21.6%) had discontinued treatment but remained in follow-up, and 63 patients (71.6%) had died; causes of death were disease progression (n = 49 [55.7%]), unknown reason (n = 9 [10.2%]), AE not related to study treatment (n = 3 [3.4%]), and other reason (n = 2 [2.3%]). In total, 26 patients (29.5%) received subsequent anticancer therapy; the most common subsequent therapies after trial discontinuation were avelumab (n = 4 [4.5%]), carboplatin and etoposide (n = 4 [4.5%]), and pembrolizumab (n = 4 [4.5%]).

Conclusions: Avelumab monotherapy led to meaningful long-term OS in a subset of patients with mMCC whose disease had progressed after chemotherapy. These results further support the role of avelumab as a standard-of-care treatment for patients with mMCC. Clinical trial information: NCT02155647

Oral
Cancer diagnosis and adverse financial events: Evidence from credit reports

Increasing evidence shows that cancer patients (pts) experience financial hardships after diagnosis. Few studies, however, have used objective financial data to estimate the relative risk of adverse financial events (AFEs) in cancer pts versus individuals without cancer. Using a retrospective case-control design, we investigated whether cancer pts are at increased risk of new AFEs, as measured by their credit reports.

Speaker
Veena Shankaran, MD
Disease/Specialty
Financial toxicity

Research Funding: Justin Butler Foundation; Texas4000 Foundation

Background: Increasing evidence shows that cancer patients (pts) experience financial hardships after diagnosis. Few studies, however, have used objective financial data to estimate the relative risk of adverse financial events (AFEs) in cancer pts versus individuals without cancer. Using a retrospective case-control design, we investigated whether cancer pts are at increased risk of new AFEs, as measured by their credit reports.

Methods: Western Washington Surveillance Epidemiology and End Results (SEER) cancer registry (cases) and voter registry (controls) records from 2013 to 2018 were linked to quarterly credit records from TransUnion (2012-2020), one of the 3 largest national credit agencies. Controls were age and sex matched to cases and assigned an index date corresponding to the diagnosis (dx) date of the matched case. Individuals with evidence of any AFE in the credit report closest to index/dx date or did not survive to 24 months were excluded. Cases and controls experiencing any of the following AFEs within 24 months were compared, using two-sample z tests: severe (3rd party collections, charge-offs), more severe (tax liens, delinquent mortgage payments), and most severe (foreclosures, repossessions). Multivariate logistic regression models were used to evaluate the association between cancer dx and AFE, adjusting for age, sex, dx year, and available credit 6 months before the index/dx date.

Results: A total of 332,825 individuals (84,185 cases and 248,640 controls, mean age 66 (SD 13), 52.7% female) were included. The mean available line of credit in the year before index/dx date was $12,303. AFEs were more common in cases versus controls (Table). After adjusting for age, sex, available credit above or below $12,303, and dx year, cancer dx was significantly associated with any AFE (OR 1.77, 95% CI 1.7-1.85, p<0.0001), severe AFEs (OR 1.94, 95% CI 1.85-2.03, p<0.0001), more severe AFEs (OR 1.23, 95% CI 1.12-1.36, p<0.0001), and most severe AFEs (OR 1.46, 95% CI 1.16-1.86, p=0.0016). Age >65 and higher available baseline credit were associated with decreased risk of any and each category of AFE.

Conclusions: Within 24 months from dx, significantly higher proportions of cancer pts experienced AFEs relative to controls. Such events on credit reports have serious and long-lasting consequences on financial status. Studies that link clinical and financial data to investigate the impacts of these events on treatment decisions, quality of life, and clinical outcomes are needed.

Optimizing Urothelial Cancer Management From Organ-Confined to Metastatic Disease: A Multidisciplinary Approach

Case Based Panel

Speaker
Evan Y. Yu, MD
Disease/Specialty
Genitourinary cancers, Multidiscplinary care

Moderated Panel Discussion with Dr. Hahn, Dr. Lee, and Dr. Vapiwala

Oral
Germline Genetic Testing for Prostate Cancer
Speaker
Colin C. Pritchard, MD, PhD
Disease/Specialty
Prostate cancer, Personalized medicine

Session Title: Prevention, Risk Reduction, and Hereditary Cancer

COG Perspective on the Impact of COVID-19 on Pediatric Oncology Clinical Trials and Implications for the Future

Education Session

Speaker
Douglas S. Hawkins, MD
Disease/Specialty
COVID-19
Poster discussion
COVID-19 and Cancer: Learning As We Go Along
Speaker
Petros Grivas, MD, PhD
Disease/Specialty
COVID-19

Session Title: Health Services Research and Quality Improvement

Poster discussion
Choosing Wisely: Selecting the Right Population at the Right Time for DNA-Damaging Therapy
Speaker
Elizabeth M. Swisher, MD
Disease/Specialty
Gynecology, Personalized medicine

Session Title: Gynecologic Cancer
 

Poster
Impact of disruptions in breast cancer control due to the COVID-19 pandemic on breast cancer mortality in the United States: Estimates from collaborative simulation modeling.

The COVID-19 pandemic has disrupted breast cancer control through short-term declines in screening, delays in diagnosis and reduced/delayed treatments. We projected the impact of COVID-19 on future breast cancer mortality.

Speaker
Kathryn P. Lowry, MD
Disease/Specialty
Breast cancer, COVID-19

Research Funding: U.S. National Institutes of Health

Background: The COVID-19 pandemic has disrupted breast cancer control through short-term declines in screening, delays in diagnosis and reduced/delayed treatments. We projected the impact of COVID-19 on future breast cancer mortality.

Methods: Three established Cancer Intervention and Surveillance Modeling Network (CISNET) models projected the impact of pandemic-related care disruptions on breast cancer mortality between 2020 and 2030 vs. pre-pandemic care patterns. Based on Breast Cancer Surveillance Consortium data, we modeled reductions in mammography screening utilization, delays in symptomatic cancer diagnosis, and reduced use of chemotherapy for women with early-stage disease for the first six months of the pandemic with return to pre-pandemic patterns after that time. Sensitivity analyses were performed to determine the effect of key model parameters, including the duration of the pandemic impact.

Results: By 2030, the models project 1,297 (model range: 1,054-1,900) cumulative excess deaths related to reduced screening; 1,325 (range: 266-2,628) deaths from delayed diagnosis of symptomatic women, and 207 (range: 146-301) deaths from reduced chemotherapy use for early-stage cancer. Overall, the models predict 2,487 (range 1,713-4,875) excess deaths, representing a 0.56% (range: 0.36%-0.99%) cumulative increase over deaths that would be expected by 2030 in the absence of the pandemic’s disruptions. Sensitivity analyses indicated that the impact on mortality would approximately double if the disruptions lasted for a 12-month period.

Conclusions: The impact of the initial pandemic-related disruptions in breast cancer care will have a small long-term cumulative impact on breast cancer mortality. The impact of the initial pandemic-related disruptions on breast cancer mortality will largely be mitigated by the rapid return to usual care. As the pandemic continues it will be important to monitor trends in care and reassess the mortality impact.

Poster discussion
Efficacy of enobosarm, a selective androgen receptor (AR) targeting agent, correlates with the degree of AR positivity in advanced AR+/estrogen receptor (ER)+ breast cancer in an international phase 2 clinical study.

The AR is expressed in up to 90% of ER+ breast cancer where it acts as a tumor suppressor. Historically, therapy with synthetic androgens had efficacy, but virilizing side effects and toxicity limited their use. Enobosarm is a selective AR activating agent that does not cause masculinization and has positive attributes such as promotion of bone and improvement of physical function. In a phase 2 study, correlation between the degree of AR staining and antitumor activity in AR+/ER+ patients with metastatic breast cancer (MBC) was examined.

Speaker
Hannah M. Linden, MD
Disease/Specialty
Breast cancer, Personalized medicine

Research Funding: Veru Inc

Background: The AR is expressed in up to 90% of ER+ breast cancer where it acts as a tumor suppressor. Historically, therapy with synthetic androgens had efficacy, but virilizing side effects and toxicity limited their use. Enobosarm is a selective AR activating agent that does not cause masculinization and has positive attributes such as promotion of bone and improvement of physical function. In a phase 2 study, correlation between the degree of AR staining and antitumor activity in AR+/ER+ patients with metastatic breast cancer (MBC) was examined.

Methods: A phase 2, open label, parallel design randomized study was conducted in 136 patients to evaluate the efficacy and safety of enobosarm in heavily pretreated women with AR+/ER+ MBC. Patients were randomized to 9 mg (n=72) or 18 mg (n=64) of oral daily enobosarm. AR expression (%AR nuclei staining) in breast cancer samples was determined centrally by immunohistochemistry. The correlation between %AR staining and clinical outcomes was examined with a focus on the 9mg dose, selected for the phase 3 study and the optimal %AR staining established.

Results: Tumor objective outcomes correlated with percent AR staining (Table). Further, using a 40% AR staining cutoff in patients with measurable disease, the clinical benefit rate (CBR) for ≥40% AR is 80% and <40% is 18% (p<0.0001). Best objective tumor response (BOR) in patients with ≥40% AR is 48% and <40% is 0% (p<0.0001). At ≥40% AR, median radiographic progression free survival (rPFS) is 5.47 and mean is 7.15 months vs <40% AR where the median rPFS is 2.72 and mean is 2.7 months. Similar %AR staining correlation was observed in the 18mg cohort. Enobosarm treatment was well tolerated with significant positive effects on quality of life measurements.

Conclusions: Enobosarm is a novel oral selective AR activating agent in which a higher % AR staining correlates with a greater antitumor activity. By targeting and activating AR, enobosarm may represent a new hormone treatment approach for AR+/ER+ MBC. The phase 3, ARTEST trial will commence in early 2021 and randomize patients with AR+/ER+/HER2- heavily treated MBC that have progressed on a non-steroidal aromatase inhibitor, fulvestrant and CDK 4/6 inhibitor to receive enobosarm or standard endocrine therapy. Clinical trial information: NCT02463032.

Poster
AMEERA-1: Phase 1/2 study of amcenestrant (SAR439859), an oral selective estrogen receptor (ER) degrader (SERD), with palbociclib (palbo) in postmenopausal women with ER+/ human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer

AMEERA-1 (NCT03284957) investigates amcenestrant, an oral SERD, as monotherapy and combined with targeted therapies in ER+/HER2– mBC. Here we report data from dose escalation (Part C) and dose expansion (Part D) of amcenestrant + palbo.

Speaker
Hannah M. Linden, MD
Disease/Specialty
Breast cancer, Personalized medicine

Research Funding: Sanofi

Background: AMEERA-1 (NCT03284957) investigates amcenestrant, an oral SERD, as monotherapy and combined with targeted therapies in ER+/HER2– mBC. Here we report data from dose escalation (Part C) and dose expansion (Part D) of amcenestrant + palbo.

Methods: Patients (pts) were postmenopausal women with ER+/HER2– mBC and ≥ 6 mos prior advanced endocrine therapy (ET) or adjuvant (adj) ET resistance (relapse on adj ET started ≥ 24 mos ago or < 12 mos after completing adj ET). Prior chemotherapy (≤ 1) for advanced disease was allowed; targeted therapies were not except ≤ 1 CDK4/6i in Part C. Part C assessed dose-limiting toxicities (DLTs) and aimed to establish the recommended phase 2 dose (RP2D) for amcenestrant (200 or 400 mg once daily [QD], in 28-day cycles) in combination with palbo (125 mg QD for 21 days on/ 7 days off). Safety (treatment-emergent adverse events [TEAEs] and lab abnormalities per CTCAE v4.03) and pharmacokinetics (PK) were evaluated. Antitumor activity at the RP2D for amcenestrant + palbo was evaluated in a subset of Part C pts and Part D, according to RECIST v1.1, determined locally by investigators.

Results: Feb 8, 2021 data cutoff. In Part C (n = 15; 200 mg: 9; 400 mg: 6), no DLTs occurred and amcenestrant 200 mg QD was selected as the RP2D with palbo, based on PK and safety data. In the pooled safety population at the RP2D (n = 39; Part C: 9; Part D: 30), median (range) age was 59 y (33–86) with ECOG PS 0 (74.4%) or 1 (25.6%) and 2 (1–6) organs involved. Immediate prior therapy was neo/adj (41.0%, all ET resistant) or advanced (59.0%, range 1–4 lines). Median (range) exposure was 32 wks (1–66) with 59.0% pts on ongoing therapy. No amcenestrant dose reductions occurred; 25.6% had ≥ 1 palbo dose reduction. Most common non-hematological TEAEs related to amcenestrant were Grade 1–2 nausea and fatigue (17.9% each), asthenia and hot flush (10.3% each); to palbo were fatigue (30.8%), nausea (25.6%), asthenia and dysgeusia (10.3% each). Two pts discontinued due to AEs. The majority (94.9%) had neutrophil count decrease (53.8% Grade ≥ 3). Preliminary antitumor activity after at least 6 cycles of therapy (unless early treatment discontinuation) is reported in the table below.

Conclusions: In pts with ER+/HER2– mBC, safety at the RP2D of amcenestrant + palbo was favorable, with no safety signals of bradycardia or eye disorders. Preliminary antitumor activity was observed (ORR: 31.4% and CBR: 74.3%). Clinical trial information: NCT03284957.

Poster discussion
Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC): Analysis of clinical and genomic subgroups from the JAVELIN Bladder 100 trial.

In the phase 3 JAVELIN Bladder 100 trial, avelumab 1L maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) vs BSC alone in patients (pts) with advanced UC that had not progressed on 1L platinum-based chemotherapy (HR, 0.69 [95% CI: 0.56, 0.86; 1-sided P= 0.0005]). We report post hoc analyses in previously unreported clinical and genomic subgroups.

Speaker
Petros Grivas, MD, PhD
Disease/Specialty
Genitourinary cancers, Metastatic/advanced

Research Funding: Funded by Pfizer as part of an alliance between Merck KGaA, Darmstadt, Germany and Pfizer

Background: In the phase 3 JAVELIN Bladder 100 trial, avelumab 1L maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) vs BSC alone in patients (pts) with advanced UC that had not progressed on 1L platinum-based chemotherapy (HR, 0.69 [95% CI: 0.56, 0.86; 1-sided P= 0.0005]). We report post hoc analyses in previously unreported clinical and genomic subgroups.

Methods: In JAVELIN Bladder 100 (NCT02603432), eligible pts had unresectable locally advanced or metastatic UC without progression after 4-6 cycles of 1L gemcitabine + cisplatin or carboplatin, and were randomized to receive avelumab + BSC (n = 350) or BSC alone (n = 350). The primary endpoint was OS, in all randomized pts and pts with PD-L1+ tumors (Ventana SP263 assay). In this exploratory analysis, we analyzed OS in disease stage and site subgroups, in pts with PD-L1+ tumors who received 1L gemcitabine + carboplatin, and in genomic subtypes (RNAseq whole-transcriptome profiling of tumor tissue) defined using data from The Cancer Genome Atlas (TCGA 2017). Interaction tests were not performed.

Results: Prolonged OS was observed in the avelumab + BSC arm vs the BSC alone arm in pts with upper or lower tract tumors, metastatic or locally advanced (LA) and unresectable disease (prior to chemotherapy), and lymph node-only disease post-chemotherapy (Table). OS was also prolonged with avelumab + BSC in pts in PD-L1+ tumors who had received 1L gemcitabine + carboplatin, consistent with findings in the overall population. In genomic subtypes, the OS benefit for avelumab + BSC was apparent across TCGA subtypes except luminal.

Conclusions: An OS benefit was seen for avelumab 1L maintenance + BSC vs BSC alone across subgroups of interest. Results are consistent with previously reported findings, further supporting avelumab 1L maintenance as a standard of care for pts with advanced UC that has not progressed with 1L platinum-containing chemotherapy. Clinical trial information: NCT02603432

Poster
Clinically advanced pelvic squamous cell carcinomas (pSCC) in men and women: A comprehensive genomic profiling (CGP) study.

Given that the clinical manifestations, disease course, and treatment options for pSCC differ between tumor types, we performed CGP to examine possible genomic differences.

Speaker
Petros Grivas, MD, PhD
Disease/Specialty
Renal, Personalized medicine

Research Funding: Foundation Medicine Inc

Background: Given that the clinical manifestations, disease course, and treatment options for pSCC differ between tumor types, we performed CGP to examine possible genomic differences.

Methods: 1,741 clinically advanced pSCCs including 230 penile (penSCC), 17 male urethral (murthSCC), 125 male anal (manSCC), 7 female urethral (furthSCC), 263 vulvar (vulSCC), 822 cervical (crvSCC), and 277 female anal SCCs (fanSCC) underwent hybrid capture-based CGP to evaluate all classes of genomic alterations (GAs). Tumor mutational burden (TMB) was determined on up to 1.1 Mb of sequenced DNA and microsatellite instability (MSI) was determined on up to 114 loci. PD-L1 expression was determined by IHC (Dako 22C3).

Results: HPV-16/18 detection was lowest in murthSCC and vulSCC and highest in manSCC, fanSCC, and crvSCC. TP53 GAs were inversely associated with HPV status. PIK3CA GA frequency varied (22-43%). DNA-damage response (DDR) GAs (e.g., BRCA1/2ATM, others) were low ( < 1-3%) throughout. Cell-cycle GAs were most frequent in external cases (penSCC, furthSCC, vulSCC). MTOR pathway GAs (PTENFBXW7) were the most frequently identified “actionable” GAs. FGFR3 GA were present in >5% of murthSCC, crvSCC, and fanSCC; other receptor-tyrosine kinase (RTK) targeted options were 1% in BRAF/ERBB2NOTCH1 GAs were present in > 15% of penSCC and vulvSCC. TMB ≥10 mut/Mb was >15% in manSCC, fanSCC, and crvSCC. PD-L1 low expression was > 25% in all pSCC except crvSCC and high expression was > 18% in all pSCC except urthSCC and manSCC.

Conclusions: Despite similar histology, pSCC differ widely in GAs and HPV status. PIK3CA is the most frequent “targetable” GA followed by MTOR pathway and cell cycle; RTK targets are extremely rare. PARP inhibitor options appear low given the infrequent finding of DDR GAs. Anti-PD(L)1 could be considered in a number of cases based on TMB>10 mut/Mb and PD-L1 expression.

Poster
Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors: An updated analysis of EV-201 Cohort 2.

Cisplatin (cis)-ineligible, platinum-naive patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC) who progress on/after anti-PD-1/L1 treatment (tx) have a poor prognosis and few tx options. Enfortumab vedotin (EV), a Nectin-4-directed antibody-drug conjugate, demonstrated overall survival (OS) benefit in pts with la/mUC who previously received anti-PD-1/L1 tx and platinum-containing chemotherapy (EV-301). EV-201 (NCT03219333) is a pivotal, single-arm, 2-cohort (C) study. C2 enrolled cis-ineligible pts with prior anti PD-1/L1 tx and no prior platinum for la/mUC. Results of the C2 primary analysis were previously presented. In this updated analysis, with 3 additional mo of follow-up (f/u), all responders were followed for ≥6 mo after onset of response.

Disease/Specialty
Genitourinary cancers, Metastatic/advanced

Research Funding: Astellas Pharma Global Development, Inc. and Seagen Inc

Background: Cisplatin (cis)-ineligible, platinum-naive patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC) who progress on/after anti-PD-1/L1 treatment (tx) have a poor prognosis and few tx options. Enfortumab vedotin (EV), a Nectin-4-directed antibody-drug conjugate, demonstrated overall survival (OS) benefit in pts with la/mUC who previously received anti-PD-1/L1 tx and platinum-containing chemotherapy (EV-301). EV-201 (NCT03219333) is a pivotal, single-arm, 2-cohort (C) study. C2 enrolled cis-ineligible pts with prior anti PD-1/L1 tx and no prior platinum for la/mUC. Results of the C2 primary analysis were previously presented. In this updated analysis, with 3 additional mo of follow-up (f/u), all responders were followed for ≥6 mo after onset of response.

Methods: Pts received 1.25 mg/kg EV on Days 1, 8, and 15 of each 28-day cycle. The primary endpoint was confirmed objective response rate (ORR) per RECIST 1.1 by blinded independent central review (BICR). Secondary endpoints were duration of response (DOR), progression-free survival (PFS), OS, and safety.

Results: 91 pts were enrolled and 89 treated in C2. Median (m) age was 75 y (range: 49-90). Pts were cis-ineligible at baseline, primarily due to CrCl < 60 mL/min (78%). Primary tumor site was upper tract in 43%, and 79% had visceral mets, including 24% with liver mets. As of 04 Dec 2020 (data cut-off), m f/u was 16.0 mo and m tx duration was 6.0 mo (range: 0.3-24.6). Confirmed ORR per BICR was 51% (95% confidence interval [CI] 39.8-61.3), including 22% complete response (CR) among treated pts. mDOR was 13.8 mo (95% CI 6.4-not reached). mPFS and mOS were 6.7 mo (95% CI 5.0-8.3) and 16.1 mo (95% CI 11.3-24.1), respectively. All-grade and grade (G) ≥3 tx-related adverse events (TRAEs) were reported in 97% and 55% of pts, respectively. Most common all-grade TRAEs were alopecia (51%), peripheral sensory neuropathy (49%), and fatigue (34%). For TRAEs ≥G3, each preferred term occurred in < 10% pts. TRAEs of interest included skin reactions (61% all grade, 17% ≥G3), peripheral neuropathy (56% all grade, 8% ≥G3), and hyperglycemia (10% all grade, 6% ≥G3). Four deaths were previously reported as tx related by investigators: 3 events ≤30 d of first EV dose (acute kidney injury, metabolic acidosis, multiple organ dysfunction syndrome) and 1 > 30 d of last EV dose (pneumonitis).

Conclusions: Efficacy and safety in this updated analysis of EV-201 C2 are consistent with the primary analysis. The majority of platinum-naive, cis-ineligible la/mUC pts who progressed on/after anti-PD-1/L1 tx responded to EV, with 22% achieving CR and mDOR exceeding a year. PFS and OS continue to be encouraging in this elderly population, with no new safety signals. These data show the potential for EV as a non-platinum option for cis-ineligible pts following anti-PD-1/L1 tx. Clinical trial information: NCT03219333

Poster
Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC) in the JAVELIN Bladder 100 trial: Subgroup analysis by duration of treatment-free interval (TFI) from end of chemotherapy to start of maintenance.

The phase 3 JAVELIN Bladder 100 trial, which enrolled patients (pts) with advanced UC that had not progressed with 1L platinum-containing chemotherapy, showed that maintenance therapy with avelumab + best supportive care (BSC) significantly prolonged overall survival (OS) compared with BSC alone (hazard ratio [HR], 0.69 [95% CI: 0.56, 0.86; 1-sided P= 0.0005]). However, the optimal timing for starting avelumab after completing 1L chemotherapy is unknown. In this post hoc analysis, we report efficacy by duration of the TFI from completion of 1L chemotherapy.

Speaker
Petros Grivas, MD, PhD
Disease/Specialty
Genitourinary cancers, Metastatic/advanced

Research Funding: Funded by Pfizer as part of an alliance between Merck KGaA, Darmstadt, Germany and Pfizer

Background: The phase 3 JAVELIN Bladder 100 trial, which enrolled patients (pts) with advanced UC that had not progressed with 1L platinum-containing chemotherapy, showed that maintenance therapy with avelumab + best supportive care (BSC) significantly prolonged overall survival (OS) compared with BSC alone (hazard ratio [HR], 0.69 [95% CI: 0.56, 0.86; 1-sided P= 0.0005]). However, the optimal timing for starting avelumab after completing 1L chemotherapy is unknown. In this post hoc analysis, we report efficacy by duration of the TFI from completion of 1L chemotherapy.

Methods: In the JAVELIN Bladder 100 trial (NCT02603432), eligible pts had unresectable locally advanced or metastatic UC without disease progression following 4 to 6 cycles of 1L platinum-containing chemotherapy. Pts were randomized to receive avelumab + BSC (n = 350) or BSC alone (n = 350) after a TFI of 4 to 10 weeks from the last dose of chemotherapy. In this exploratory analysis, subgroups with a TFI of 4 to < 6 weeks ( < 42 days), 6 to < 8 weeks (42 to < 56 days), or 8 to 10 weeks (≥56 days) were evaluated.

Results: In the avelumab + BSC and BSC alone arms, the TFI was 4 to < 6 weeks in 143 and 158 pts, 6 to < 8 weeks in 109 and 80 pts, and 8 to 10 weeks in 98 and 110 pts, respectively. Baseline characteristics in these subgroups were generally well balanced between arms. For both arms combined, however, the TFI 4 to < 6 weeks subgroup vs the other 2 subgroups included more pts with visceral metastases (57.8% vs 54.0% and 50.0%), an objective response with 1L chemotherapy (76.4% vs 69.3% and 68.3%), and an ECOG performance status of 1 (44.5% vs 33.3% and 35.6%). OS was prolonged with avelumab + BSC vs BSC alone in all subgroups; the HR was 0.76 (95% CI: 0.546, 1.059) in the TFI 4 to < 6 weeks subgroup (median OS, 19.9 months [95% CI: 16.3, 25.3] vs 13.5 months [95% CI: 11.7, 17.4]), 0.64 (95% CI: 0.404, 1.021) in the TFI 6 to < 8 weeks subgroup (median OS, 26.1 months [95% CI: 19.9, not estimable] vs 21.0 months [95% CI: 10.7, not estimable]), and 0.70 (95% CI: 0.468, 1.035) in the TFI 8 to 10 weeks subgroup (median OS, 20.1 months [95% CI: 13.8, not estimable] vs 14.1 months [95% CI: 11.7, 19.6]).Conclusions:In patients with advanced UC that had not progressed with 1L platinum-containing chemotherapy, avelumab 1L maintenance prolonged OS irrespective of the TFI assessed in this study (4-10 weeks), supporting this new treatment strategy as a standard of care. Differences in duration of TFI were likely related to individual patient- and disease-specific characteristics or logistics and did not impact the OS benefit observed with avelumab 1L maintenance. Clinical trial information: NCT02603432

Poster discussion
Efficacy of clinical breast examination in chest-irradiated female survivors of childhood Hodgkin lymphoma (HL).

Female survivors of childhood HL treated with ≥10 Gy of chest radiation are at high risk for breast cancer (BC). The Children’s Oncology Group (COG) guidelines recommend CBE annually starting at puberty and then semiannually from age 25, plus lifetime annual mammography (MAM) and breast Magnetic Resonance Imaging (MRI) starting 8y after chest radiation or age 25, whichever is later. While imaging-based screening recommendations are largely consistent with US guidelines for women at high BC risk, only the COG guidelines recommend CBE. The benefits of lifetime CBE starting from puberty for life in chest-irradiated HL survivors is unknown.

Speaker
Janie M. Lee, MD, MSc
Disease/Specialty
Breast cancer, Screening/prevention

Research Funding: American Cancer Society, U.S. National Institutes of Health

Background: Female survivors of childhood HL treated with ≥10 Gy of chest radiation are at high risk for breast cancer (BC). The Children’s Oncology Group (COG) guidelines recommend CBE annually starting at puberty and then semiannually from age 25, plus lifetime annual mammography (MAM) and breast Magnetic Resonance Imaging (MRI) starting 8y after chest radiation or age 25, whichever is later. While imaging-based screening recommendations are largely consistent with US guidelines for women at high BC risk, only the COG guidelines recommend CBE. The benefits of lifetime CBE starting from puberty for life in chest-irradiated HL survivors is unknown.

Methods: Life-years (LYs) and lifetime BC mortality risk were estimated from a simulated cohort of 5-million HL survivors using the data from 5y female survivors of HL in the Childhood Cancer Survivor Study (CCSS) treated with ≥10 Gy of chest radiation. The simulated cohort underwent annual MAM+MRI from age 25 for life, with and without annual CBE from age 11 (presumed age of puberty) to age 24 and with and without semiannual CBE from age 25 for life with 100% adherence. BC included in-situ and invasive BC. Treatment-related BC incidence and non-BC mortality risks were estimated from the CCSS data. Risks at age <25 were extrapolated from the CCSS estimates while risks beyond age 50 were extrapolated additionally using the US population rates. CBE sensitivity (17.8%, in-situ and invasive BC) and specificity (98%) and MAM+MRI sensitivity (84.2-86.0%, in-situ; 96.7-97.1%, invasive) and specificity (75.3%) were obtained from the medical literature.

Results: The CCSS cohort included 1057 female HL survivors. BC (all invasive) developed in three patients at age <25 (ages: 23, 24, 24). In the simulated cohort receiving no screening, lifetime BC risk was 40.8% and BC mortality was 17.5%. HL survivors around age 50 were at a 7.4-fold higher risk of developing BC and a 5.2-fold higher risk of non-BC mortality when compared with the general population. Compared to no annual CBE for ages 11-24y, undergoing annual CBE did not increase gains in LYs or reduce lifetime BC mortality relative to no screening (Table). Among those who survived to age ≥25, undergoing semiannual CBE from age 25 for life compared to no semiannual CBE also resulted in little gain in LYs or reduction in lifetime BC mortality relative to no screening.

Conclusions: Lifetime CBE starting at puberty in conjunction with MAM+MRI appears to add little survival benefits compared with no CBE, suggesting that COG guidelines may be revised without adverse effect on long-term outcomes for chest-irradiated female survivors of childhood HL.

Poster
Phase 1b dose escalation study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of GS-3583, a FLT3 agonist Fc fusion protein, in patients with advanced solid tumors.

Productive antitumor immune responses in nonclinical models depend on a type of dendritic cell (DC), conventional DC subtype 1 (cDC1), which in the context of cancer, primes tumor-reactive T cells through presentation of tumor-derived antigens. FMS-related tyrosine kinase 3 ligand (FLT3L) is a hematopoietic growth factor that binds to and activates FLT3 on terminally differentiated DCs. Activated FLT3 promotes proliferation, inhibits cell death, and is required for the differentiation, expansion, and maintenance of DCs in peripheral and lymphoid organs. GS-3583 is a fusion protein composed of the extracellular domain of recombinant human FLT3L fused to an engineered fragment crystallizable (Fc) region of human immunoglobulin G4. GS-3583 has PK properties that support sustained cDC in patients and potential combination with established immunotherapies. This phase 1b, open-label, multicenter, dose-finding study will evaluate safety, tolerability, PK, and preliminary efficacy of GS-3583 monotherapy in patients with advanced solid tumors (NCT04747470).

Speaker
John A. Thompson, MD
Disease/Specialty
Phase 1 Program, Personalized medicine

Research Funding: Gilead Sciences, Inc

Background: Productive antitumor immune responses in nonclinical models depend on a type of dendritic cell (DC), conventional DC subtype 1 (cDC1), which in the context of cancer, primes tumor-reactive T cells through presentation of tumor-derived antigens. FMS-related tyrosine kinase 3 ligand (FLT3L) is a hematopoietic growth factor that binds to and activates FLT3 on terminally differentiated DCs. Activated FLT3 promotes proliferation, inhibits cell death, and is required for the differentiation, expansion, and maintenance of DCs in peripheral and lymphoid organs. GS-3583 is a fusion protein composed of the extracellular domain of recombinant human FLT3L fused to an engineered fragment crystallizable (Fc) region of human immunoglobulin G4. GS-3583 has PK properties that support sustained cDC in patients and potential combination with established immunotherapies. This phase 1b, open-label, multicenter, dose-finding study will evaluate safety, tolerability, PK, and preliminary efficacy of GS-3583 monotherapy in patients with advanced solid tumors (NCT04747470).

Methods: Approximately 33 adults aged ≥18 years with a histologically or cytologically confirmed locally advanced or metastatic malignant solid tumor that is refractory to or intolerant of standard therapy or for which no standard therapy is available will be enrolled. The study employs a 3+3 dose escalation design in which GS-3583 is administered intravenously for up to 52 weeks or until progressive disease or unacceptable toxicity. Up to five dose escalation cohorts have been planned. The maximum tolerated dose is the highest dose with incidence of DLT in < 33% of 6 or more patients in the first 28 days of GS-3583 dosing; recommended phase 2 dose will be determined. Assessments include safety, PK, pharmacodynamics including cDCs, immunogenicity, and efficacy by RECIST 1.1 in CT/MRI imaging conducted every 8 weeks. Accrual at approximately 3-4 centers in the US is ongoing. Clinical trial information: NCT04747470

Poster discussion
Safety and efficacy outcomes with nivolumab plus ipilimumab in patients with advanced renal cell carcinoma and brain metastases: results from the CheckMate 920 trial.

Combination therapy with nivolumab plus ipilimumab (NIVO+IPI) has demonstrated long-term efficacy and tolerability in patients with previously untreated advanced renal cell carcinoma (aRCC). Previous phase 3 clinical trials of patients with advanced or metastatic cancers have mostly excluded patients with brain metastases. CheckMate 920 is an ongoing, phase 3b/4 clinical trial of NIVO+IPI treatment in patients with aRCC with a high unmet medical need. We present updated safety and efficacy results for the cohort of patients with aRCC of any histology and brain metastases from CheckMate 920 (NCT02982954).

Speaker
Scott S. Tykodi, MD, PhD
Disease/Specialty
Genitourinary cancers, Metastatic/advanced

Research Funding: Bristol Myers Squibb

Background: Combination therapy with nivolumab plus ipilimumab (NIVO+IPI) has demonstrated long-term efficacy and tolerability in patients with previously untreated advanced renal cell carcinoma (aRCC). Previous phase 3 clinical trials of patients with advanced or metastatic cancers have mostly excluded patients with brain metastases. CheckMate 920 is an ongoing, phase 3b/4 clinical trial of NIVO+IPI treatment in patients with aRCC with a high unmet medical need. We present updated safety and efficacy results for the cohort of patients with aRCC of any histology and brain metastases from CheckMate 920 (NCT02982954).

Methods: Patients with previously untreated advanced/metastatic aRCC of any histology, with asymptomatic brain metastases (not currently receiving corticosteroids or radiation), and Karnofsky performance status ≥ 70% were assigned to treatment with NIVO 3 mg/kg + IPI 1 mg/kg every 3 weeks × 4 doses followed by NIVO 480 mg every 4 weeks for ≤ 2 years or until disease progression/unacceptable toxicity. The primary endpoint was incidence of grade ≥ 3 immune-mediated adverse events (imAEs) within 100 days of last dose of study drug. Key secondary endpoints included progression-free survival (PFS) and objective response rate (ORR) by RECIST v1.1 (both per investigator). Exploratory endpoints included overall survival (OS).

Results: Of 28 treated patients with brain metastases, 85.7% were men; median (range) age was 60 (38–87) years, and 14.3% had sarcomatoid features. With 24.5 months minimum follow-up of the 28 patients enrolled, median duration of therapy (range) was 3.4 (0.0–23.3) months for NIVO and 2.1 (0.0–3.3) months for IPI. No grade 5 imAEs occurred. Grade 3–4 imAEs by category were diarrhea/colitis (7.1%), hypophysitis (3.6%), rash (3.6%), hepatitis (3.6%), and diabetes mellitus (3.6%). Of the 25 patients who were evaluable for ORR, the ORR was 32.0% (95% CI, 14.9–53.5). No patients achieved complete response, 8 achieved partial response, and 10 patients had stable disease. Median time to response (range) was 2.8 (2.4–3.0) months. Median duration (range) of response was 24.0 (3.9–not estimable [NE]) months; 4 of 8 responders remain without reported progression. Of 28 patients, 7 (25%) had intracranial progression. Median PFS (n = 28) was 9.0 (95% CI, 2.9–12.0) months. Median OS (n = 28) was still not reached (95% CI, 14.1 months–NE).

Conclusions: In patients with previously untreated aRCC and brain metastases, a population with high unmet medical need that is often underrepresented in clinical trials, the approved treatment regimen of NIVO+IPI followed by NIVO for aRCC showed no new safety signals and continues to show encouraging antitumor activity with longer follow-up. Clinical trial information: NCT02982954

Poster
Disparity in telehealth and emergency department use among Medicaid and commercially insured patients receiving systemic therapy for cancer in Washington State following the COVID-19 Pandemic.

Washington was the first US state to experience the COVID-19 pandemic. Transmission risks and patient fears of visiting oncology practices during its onset resulted in rapid adoption of telehealth services. We hypothesized that the pandemic would widen disparities in oncology practice visits between Medicaid and commercially insured patients, resulting higher rates of emergency department (ED) visits during initial treatment.

Speaker
Veena Shankaran, MD
Disease/Specialty
COVID-19

Research Funding: U.S. National Institutes of Health

Background: Washington was the first US state to experience the COVID-19 pandemic. Transmission risks and patient fears of visiting oncology practices during its onset resulted in rapid adoption of telehealth services. We hypothesized that the pandemic would widen disparities in oncology practice visits between Medicaid and commercially insured patients, resulting higher rates of emergency department (ED) visits during initial treatment.

Methods: Linking Washington State SEER records with Medicaid and commercial insurance enrollment and claims records, we compared adults age <65 with new solid tumor malignancies who received systemic treatment at academic and community oncology practices. Persons starting therapy March – June 2020 (COVID) were compared with those starting therapy March-June 2017-2019 (Pre-COVID). Poisson regressions were used to evaluate differences in oncology practice office visits and telehealth visits. Logistic regressions were used to evaluate the likelihood of at least one ED admission among patients starting systemic therapy pre- and post-COVID.

Results: Among patients who met inclusion criteria (652 Commercial, 349 Medicaid), Medicaid enrollees had more advanced disease and more comorbidity versus commercial enrollees. In unadjusted analysis of E&M and telehealth service visit codes, office-based visits fell for both insurance groups (Table) while telehealth service visits (negligible pre-COVID) were higher for commercial versus Medicaid enrollees post-COVID. The proportion of persons with ≥ 1 ED visit during therapy fell for both insurance groups. In Poisson models, Medicaid enrollees had significantly fewer total visits (P=0.001) and fewer telehealth visits (p<0.001) compared commercial enrollees during the COVID period. In the logit models, ED visits trended lower for both groups after COVID (OR 0.53 95% CI 0.279 to 1.008). Among Medicaid enrollees, persons ages 40-49 and breast cancer patients were more likely to visit the ED. Among the commercially insured, persons with 2 or more comorbidities were more likely to visit the ED. The pre-post COVID change in likelihood of an ED visit was not significantly different between insurance groups (p=0.355).

Conclusions: In Washington State, the COVID-19 pandemic created a substantial disparity in access to office-based and telehealth care for low-income patients receiving systemic therapy for new cancers. Reduced oncology practice visits among Medicaid patients did not widen existing disparities in utilization of emergency care.

Poster
Initial report on hospitalized cancer patients with COVID-19 from the National Cancer Institute (NCI) COVID-19 in Cancer Patients Study (NCCAPS).

Hospitalized cancer patients (pts) with COVID-19 have a severe disease course and high mortality. Pts with lung cancer, hematologic malignancies and metastatic disease may be at higher risk. Detailed prospective inpatient data may help to identify those at greatest risk for poor outcomes.

Speaker
Steven A. Pergam, MD, MPH
Disease/Specialty
COVID-19

Research Funding: U.S. National Institutes of Health

Background: Hospitalized cancer patients (pts) with COVID-19 have a severe disease course and high mortality. Pts with lung cancer, hematologic malignancies and metastatic disease may be at higher risk. Detailed prospective inpatient data may help to identify those at greatest risk for poor outcomes.

Methods: NCCAPS is a longitudinal study aiming to accrue 2,000 cancer pts undergoing treatment for hematologic malignancy or solid tumor with COVID-19. For pts’ first COVID-19 hospitalization, clinical data, research blood specimens and imaging are collected, and additional clinical data are collected during subsequent hospitalizations.

Results: As of Jan. 22, 2021, among 757 enrolled adult patients from 204 sites, 124 (16.3%) reported at least one hospitalization for COVID-19, and discharge data was available for 98 hospitalizations in 88 patients. The median age was 67 (range 21-93, 1Q:56, 3Q:72), 35/88 (40%) were female. The most common malignancies in hospitalized adult pts were lymphoma (18.2%), lung cancer (15.9%) and multiple myeloma (10.2%). The most common presenting symptoms were shortness of breath (65%), fatigue/malaise (64%), and fever (49%). 8/88 (9%) pts were neutropenic (ANC < 1000) at presentation; 17/88 (19%) were thrombocytopenic. Median length of stay was 6.5 days (range 1-41, 1Q:4, 3Q:12). Among those hospitalized, 20/88 (22.7%) received care in the ICU or high dependency unit, with a median ICU stay of 7 days (range 1-22, 1Q:2.5, 3Q:9.5); of those admitted to the ICU, 25% (5/20) received invasive mechanical ventilation. Of those in whom inpatient medications were recorded (n = 63), 63% received corticosteroids, 46% received remdesivir, and 14% received convalescent plasma. One pt received bamlanivimab and 2 patients received tocilizumab. Most (46/63; 73%) received anticoagulation, primarily prophylactic low molecular weight heparin; 11/63 (17%) received therapeutic dose anticoagulation. Inpatient D-dimer values were recorded in 43 inpatients, 26 of whom had multiple measurements. 16/98 hospitalizations ended with death (16%).

Conclusions: Preliminary analysis of NCCAPS data reveals that inpatient hospital admission is common among oncology patients with COVID-19 and mortality rates appear high within this cohort. Hematologic malignancies and lung cancer are the most common underlying diagnoses in patients requiring hospitalization. Corticosteroids and anti-coagulation were the most commonly used therapies. Despite high rates of ICU admission, invasive mechanical ventilation may be instituted less often in an oncology cohort. These observations may inform decisions about vaccine policy and decisions to limit life sustaining treatment. Clinical trial information: NCT04387656

Poster
Code status and outcomes in patients with cancer and COVID-19: A COVID-19 and cancer consortium (CCC19) registry analysis.

In-hospital mortality among patients with cancer (pts) and COVID-19 infection is high. The frequency of, and factors associated with, do-not-resuscitate (DNR) or do-not-intubate (DNI) orders at hospital admission (HA), and their correlation with care, has not been well studied. In November 2020, we began collecting this information for pts who were hospitalized at initial presentation in the CCC19 registry (NCT04354701).

Speaker
Elizabeth T. Loggers, MD, PhD
Disease/Specialty
COVID-19

Research Funding: P30 CA068485

Background: In-hospital mortality among patients with cancer (pts) and COVID-19 infection is high. The frequency of, and factors associated with, do-not-resuscitate (DNR) or do-not-intubate (DNI) orders at hospital admission (HA), and their correlation with care, has not been well studied. In November 2020, we began collecting this information for pts who were hospitalized at initial presentation in the CCC19 registry (NCT04354701).

Methods: We investigated: 1. the frequency of, and factors associated with, DNR/DNI orders at HA; 2. change in code status during HA; and 3. the correlation between DNR/DNI orders and palliative care consultation (PC), mortality or length of stay (LOS). We included hospitalized, adult pts with cancer and COVID-19 from 57 participating sites. Reported characteristics include age, ECOG performance status (PS), and cancer status. Comparative statistics include 2-sided Wilcoxon rank sum and Fisher’s exact tests.

Results: 744 pts had known baseline and/or changed code status (CS); most (79%) maintained their baseline CS (Table). Those with DNR±DNI orders at HA were older (median age 79 vs 69 yrs, p<0.001) and more likely to have: ECOG PS 2+ vs 0-1 (45% vs 22%, OR 3.95, p<0.001), metastatic disease (45% vs 35%, OR 1.72, p=0.005) and progressing cancer (32% vs 16%, OR 2.69, p<0.001), but equally likely to have received systemic anticancer therapy in the prior 3 months (38% vs 45%, p=0.15). N=192 pts with a change in CS from full to DNR±DNI were younger (median age 73), had better PS (37% ECOG PS 2+), and were less likely to have progressing cancer (23%) than those with DNR±DNI orders at baseline. However, their LOS was significantly longer, median 9 vs 6 days, p<0.001. Compared to those with DNR±DNI orders at HA, pts whose CS changed to DNR±DNI were more likely to die, OR 2.94, 95% CI 1.76-4.97, p<0.001. PC was obtained in 106 (14%) pts and associated with transition to DNR±DNI in 47 (44%), affirmation of admission CS in 58 (55%), and reversal in 1 (1%). Median LOS for pts receiving PC was 11 vs 6 days, p<0.001.

Conclusions: In our sample, the majority of patients with cancer and COVID-19 were full code at hospital admission. DNR±DNI status, whether at baseline or assigned during the hospital course, was associated with worse prognosis. Longer length of stay for patients changing code status and/or receiving palliative care consultation was observed likely suggesting earlier palliative care consultation is an important, but likely underutilized component in the care of patients with cancer and COVID-19.

Poster
Efficacy and cost-effectiveness of breast cancer (BC) screening in female survivors of childhood Hodgkin lymphoma (HL).

Female childhood HL survivors treated with ≥10 Gy of chest radiation are at high risk of developing BC. The Children’s Oncology Group (COG) guidelines recommend lifetime annual mammography (MAM) and breast Magnetic Resonance Imaging (MRI) starting 8y after chest radiation or age 25, whichever is later, and clinical breast examination (CBE) annually from puberty and semiannually from age 25. Initial model results suggest that CBE adds no survival benefit in this cohort. Digital breast tomosynthesis (DBT) is increasingly replacing digital MAM in clinical practice. Here, we present the efficacy and cost-effectiveness of COG’s imaging-based screening recommendations.

Speaker
Janie M. Lee, MD, MSc
Disease/Specialty
Breast cancer

Research Funding: American Cancer Society, U.S. National Institutes of Health

Background: Female childhood HL survivors treated with ≥10 Gy of chest radiation are at high risk of developing BC. The Children’s Oncology Group (COG) guidelines recommend lifetime annual mammography (MAM) and breast Magnetic Resonance Imaging (MRI) starting 8y after chest radiation or age 25, whichever is later, and clinical breast examination (CBE) annually from puberty and semiannually from age 25. Initial model results suggest that CBE adds no survival benefit in this cohort. Digital breast tomosynthesis (DBT) is increasingly replacing digital MAM in clinical practice. Here, we present the efficacy and cost-effectiveness of COG’s imaging-based screening recommendations.

Methods: Life-years (LYs), quality-adjusted LYs (QALYs), BC mortality, and costs (2017 U.S.$) were estimated from simulating the lifetimes of 5-million chest-irradiated 25y old HL survivors who underwent BC screening with each of the following strategies: annual digital MAM, MRI, MAM+MRI, annual DBT or DBT+MRI from age 25 onward. Treatment-related BC risk (in-situ and invasive) and non-BC mortality were estimated from female 5y HL survivors in the Childhood Cancer Survivor Study and from U.S. population rates. Test sensitivity was 70-74% for MAM (based on prior HL studies) and 89% for DBT and MRI (based on women at high risk of de novo BC). Costs and quality of life weights were obtained from medical literature.

Results: For HL survivors with no screening, lifetime BC risk was 42.7% and BC mortality was 18.1%. BC risk and non-BC mortality were, respectively, 7.4- and 5.2-fold higher at age 50 in HL survivors relative to the general population. Screening at ages 25-74 had similar LY gain and BC mortality reduction compared to lifetime screening; hence, we focused on screening for ages 25-74. For all strategies screening provided LY gain of 0.34-0.47 and reduced BC mortality by 6.7-9.8% compared with no screening; incremental cost-effectiveness ratio (ICER), or cost per QALY gained, for MAM alone was $58,726 and for DBT alone was $62,989. ICER of adding MRI to MAM ($385,285) or to DBT ($513,358) indicated lower cost-effectiveness of supplemental MRI (Table).

Conclusions: Annual screening at ages 25-74y in chest-irradiated HL survivors appears beneficial. Using $100K per QALY gained as cost-effectiveness threshold, annual MAM or DBT are more cost-effective, whereas adding MRI to MAM is less cost-effective.

Poster
Health-related unemployment trends among survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).

The impact of treatment era and chronic health conditions on health-related unemployment among childhood cancer survivors has not been studied.

Speaker
Neel S. Bhatt, MBBS, MPH
Disease/Specialty
Pediatric oncology

Research Funding: U.S. National Institutes of Health

Background: The impact of treatment era and chronic health conditions on health-related unemployment among childhood cancer survivors has not been studied.

Methods: Childhood cancer survivors (age ≥25 years) enrolled in the CCSS (3,420 diagnosed in the 1970s, 3,564 in the 1980s, and 2,853 in the 1990s) were matched 1:5 on sex, race/ethnicity, census bureau division, age, and year of survey to the Behavioral Risk Factor Surveillance System (BRFSS), a nationally representative population. Among survivors, health-related unemployment was defined as self-reported unemployment due to illness/disability and for BRFSS participants as self-reported inability to work. To standardize follow-up, health-related unemployment was assessed either in 2002-05 or 2014-16 for both cohorts. Sex stratified standardized prevalence ratio (SPR) and relative SPR (rSPR) with 95% confidence intervals (CI) for health-related unemployment were estimated using multivariable generalized linear models, with BRFSS background rates to assess the impact of treatment era and moderate to severe health conditions (per the Common Terminology Criteria for Adverse Events).

Results: Prevalence of health-related unemployment in survivors (median age 9 years [range 0-20] at diagnosis and 33 years [25-54] at follow-up) was significantly higher compared to BRFSS participants (females: 11.3% vs 3.7%; SPR 3.0, 95% CI 2.7-3.3; males: 10.5% vs 3.0%; SPR 3.5, 95% CI 3.1-3.9). Health-related unemployment risks declined among survivors in more recent decades (ptrend< 0.001) for females: 1970s SPR 3.8, 95% CI 3.2-4.5, 1980s SPR 2.9, 95% CI 2.5-3.5, 1990s SPR 2.5, 95% CI 2.1-3.0; and males: 1970s SPR 3.6, 95% CI 2.9-4.4, 1980s SPR 3.8, 95% CI 3.1-4.7, 1990s SPR 3.0, 95% CI 2.5-3.7. Among survivors, multivariable models identified associations between presence of specific health conditions and elevated health-related unemployment (Table) adjusting for all statistically significant health conditions, race/ethnicity, treatment era, age at survey, and diagnosis. Among females, rSPR for endocrine conditions differed between 1970s and 1990s (interaction p = 0.04); fewer significant health conditions remained in the final model for males.

Conclusions: While prevalence for health-related unemployment has declined over time, childhood cancer survivors remain at higher risk compared to the general population. These elevated risks are associated with chronic health conditions and affect female survivors more than male survivors.

8:00 AM
Oral
First-in-human phase I/II study of CYT-0851, a first-in-class inhibitor of RAD51-mediated homologous recombination in patients with advanced solid and hematologic cancers.

Homologous recombination (HR) is an essential, high-fidelity mechanism to repair DNA double strand breaks (DSBs). Inhibition of HR in cancer cells leads to accumulation of unrepaired DSBs and tumor cell death. This is the first reporting of the first-in-human study of CYT-0851, an oral, first-in-class, small molecule inhibitor of RAD51-mediated DNA repair.

Speaker
Ryan Lynch, MD
Disease/Specialty
Personalized medicine

Research Funding: Cyteir Therapeutics

Background: Homologous recombination (HR) is an essential, high-fidelity mechanism to repair DNA double strand breaks (DSBs). Inhibition of HR in cancer cells leads to accumulation of unrepaired DSBs and tumor cell death. This is the first reporting of the first-in-human study of CYT-0851, an oral, first-in-class, small molecule inhibitor of RAD51-mediated DNA repair.

Methods: Patients (pts) with advanced hematologic and solid tumors were treated with continuous 28-day cycles of increasing doses of CYT-0851 with an accelerated titration and 3+3 trial design. Primary objectives included safety, maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D) (Phase 1), and antitumor activity (Phase 2). Secondary and exploratory objectives included pharmacokinetics (PK), pharmacodynamics (PD) and predictive biomarkers of response.

Results: As of an 8 Dec 2020 data cutoff (DCO), 23 pts with advanced cancers (Sarcoma n = 8, Breast n = 4, Non-Hodgkin’s Lymphoma n = 5; Pancreas n = 3; Ovarian n = 2; mucoepidermoid carcinoma n = 1) were enrolled in 6 cohorts (15 mg, 20 mg, 30 mg, and 45 mg BID; 90 mg and 130 mg QD). No pts experienced a dose-limiting toxicity and escalation continues per protocol to identify the MTD. 6 pts (26.1%) experienced a CYT-0851-related adverse event with only Gr 1/2 nausea (n = 3, 13%) and constipation (n = 2, 8.7%) occurring in > 1 pt. There has been no reported CYT-0851-related myelosuppression, serious adverse events, study discontinuation, or death. Preliminary PK analyses showed dose proportional systemic exposure with a half-life of ̃3 days supporting transition from BID to QD dosing. PD effects were observed with increases in ɣH2AX in on-treatment circulating tumor cells compared to baseline at exposures associated with preclinical anti-tumor activity. Ten pts were response evaluable prior to the DCO. Two partial responses by Lugano and RECIST v1.1 criterion were achieved in pts with DLBCL (-74%) and myxofibrosarcoma (-30%) at 45 mg BID with treatment ongoing at 126+ and 250+ days. An additional two pts, with pancreatic cancer (-19%) and follicular lymphoma (-42%) had stable disease with tumor shrinkage at 45 mg BID for 111 and 99+ days.

Conclusions: CYT-0851, a first-in-class inhibitor of RAD51-mediated HR, is well tolerated, with linear PK, target-directed PD effects and promising antitumor activity across different tumor types. CYT-0851 is the first DNA-damage repair (DDR) therapeutic with demonstrated clinical activity in both hematologic malignancies and solid tumors. Dose escalation continues to establish the RP2D, with planned expansion in 7 disease-specific cohorts in hematologic and solid cancers. Clinical trial information: NCT03997968

10:00 AM
Oral
Efficacy and safety of patritumab deruxtecan (HER3-DXd) in EGFR inhibitor-resistant, EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC).

Patients (pts) with advanced EGFRm NSCLC have limited treatment options after failure of EGFR TKI and platinum-based chemotherapy (PBC). HER3-DXd is an antibody drug conjugate consisting of a fully human monoclonal antibody to HER3 attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. We previously presented efficacy/safety data (median follow-up, 5.4 mo) from an ongoing study of HER3-DXd in EGFRm NSCLC after failure of EGFR TKI therapy. We now present extended follow-up of pts receiving the recommended dose for expansion (5.6 mg/kg IV Q3W).

Speaker
Christina S. Baik, MD, MPH
Disease/Specialty
Lung cancer, Personalized medicine

Research Funding: Daiichi Sankyo, Inc

Background: Patients (pts) with advanced EGFRm NSCLC have limited treatment options after failure of EGFR TKI and platinum-based chemotherapy (PBC). HER3-DXd is an antibody drug conjugate consisting of a fully human monoclonal antibody to HER3 attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. We previously presented efficacy/safety data (median follow-up, 5.4 mo) from an ongoing study of HER3-DXd in EGFRm NSCLC after failure of EGFR TKI therapy. We now present extended follow-up of pts receiving the recommended dose for expansion (5.6 mg/kg IV Q3W).

Methods: This Ph 1 dose-escalation/expansion study included pts with locally advanced or metastatic EGFRm NSCLC with prior EGFR TKI therapy (NCT03260491). Pts with stable brain metastases (BM) were allowed. The primary endpoint was confirmed ORR by blinded independent central review (BICR) per RECIST v1.1; secondary endpoints included DOR, PFS and safety.

Results: At data cutoff (Sept 24, 2020), 57 pts were treated with HER3-DXd 5.6 mg/kg IV Q3W; median follow-up, 10.2 mo (range, 5.2-19.9 mo). Median number of prior anticancer regimens was 4 (range, 1-10). 100% had prior EGFR TKI (86% prior osimertinib [OSI]) and 91% had prior PBC. 47% had a history of BM. Median treatment duration was 5.5 mo (range, 0.7-18.6 mo); treatment was ongoing in 18 pts (32%). Confirmed ORR by BICR was 39% (22/57; 95% CI, 26.0%-52.4%; 1 CR, 21 PR, 19 SD) with 14/22 responses occurring within 3 mo of starting HER3-DXd. DCR was 72% (95% CI, 58.5%-83.0%). Median DOR was 6.9 mo (95% CI, 3.1 mo-NE), and median PFS was 8.2 mo (95% CI, 4.4-8.3 mo). Antitumor activity was observed across diverse mechanisms of EGFR TKI resistance, including those not directly related to HER3 (EGFR C797S, MET or HER2 amp, and BRAF fusion). Among pts with prior PBC, ORR was 37% (19/52; 95% CI, 23.6%-51.0%); in pts with prior OSI and PBC, ORR was 39% (17/44; 95% CI, 24.4%-54.5%). Among 43 pts evaluable for HER3 expression, nearly all expressed HER3; median membrane H-score by IHC was 180 (range, 2-280). Median H-score (range; N) was 195 (92-268; 15) in pts with CR/PR, 180 (4-280; 15) with SD, 126.5 (2-251; 6) with PD, and 180 (36-180; 7) in pts unevaluable for best overall response. The most common grade ≥3 adverse events (AEs) were thrombocytopenia (30%), neutropenia (19%), and fatigue (14%). Drug-related interstitial lung disease by central adjudication occurred in 4 pts (7%; 1 grade ≥3 [2%]; no grade 5). 6/57 pts (11%) had AEs associated with treatment discontinuation (none were due to thrombocytopenia).

Conclusions: HER3-DXd 5.6 mg/kg IV Q3W demonstrated antitumor activity across various EGFR TKI resistance mechanisms in heavily pretreated metastatic/locally advanced EGFRm NSCLC. The safety profile was consistent with previous reports. A Ph 2 study of HER3-DXd in pts with EGFRm NSCLC after failure of EGFR TKI and PBC has been initiated (NCT04619004). Clinical trial information: NCT03260491

Sunday, June 6th
5:00 AM
Oral
Emerging Trends in Radiation for Localized Lung Cancers
Speaker
Ramesh Rengan, MD, PhD
Disease/Specialty
Thoracic cancers, Personalized medicine

Abstracts Discussion 3

Tuesday, June 8th
8:30 AM
Optimizing Precision Therapy in Salivary Gland Cancers With a Look at the Future

Case Based Panel

Speaker
Cristina P. Rodriguez, MD
Disease/Specialty
Head and neck cancers, Personalized medicine

Speakers

More than 20 members of our leading-edge research team will be sharing their latest findings. Here are some of the highlights.

Clinical trials

SCCA has one of the most active clinical trial programs in the world - providing new hope for our patients every day. We currently have more than 400 clinical trials open for patients.