Highlights from the 2021 San Antonio Breast Cancer Symposium
Chemotherapy is not necessary for postmenopausal women with node-positive, ER+, HER- breast cancer and a low recurrence score, according to a recently published peer-reviewed study (RxPONDER). The study was discussed in December at the 44th San Antonio Breast Cancer Symposium (SABCS), along with other developments in breast cancer research.
“We saw exciting results from several clinical trials that impact care in community oncology settings,” says Dr. Hannah Linden, SCCA physician and Professor of Medical Oncology at the University of Washington School of Medicine. In addition to RxPONDER, they include:
- MA.32: Metformin does not prevent recurrence of early breast cancer.
- Keynote 522: Pembrolizumab is an effective addition to chemotherapy for high-risk, early-stage, triple negative breast cancer.
- DESTINY: Trastuzumab deruxtecan (T-DXd) outperforms ado-trastuzumab emtansine (TDM-1) as a second line treatment in patients with HER2+ breast cancer.
Other promising diagnostics and therapies presented at SACBS remain in the clinical trial stage. Some currently available at SCCA are:
- Pembrolizumab for patients with metastatic, PD-L1 negative, triple negative breast cancer
- Patritumab deruxtecan (HER3-DXd), a HER3-targeted antibody drug conjugate, for patients with metastatic triple negative breast cancer
- Oral selective estrogen receptor down-modulators (SERDs) for patients with ER+ metastatic breast cancer
- PET imaging with F-18-fluoroestradiol (FES) in patients with ER+ metastatic breast cancer to help determine whether oral SERDs block ER uptake, as an imaging biomarker prior to treatment start, and for diagnostic dilemmas.
Dr. Linden offers a deeper look into these advances in breast cancer care and research with six highlights from the SABCS:
1. Chemotherapy Benefit Depends on Menopausal Status in Node-Positive Breast Cancer With Low Recurrence Scores
The RxPONDER trial looked at endocrine therapy vs. endocrine therapy plus chemotherapy in women with early breast cancer. Study participants had:
- ER+, HER2- breast cancer
- One to three positive axillary lymph nodes
- Recurrence score of 25 or lower based on the Oncotype DX® genomic test
Interim results, which were simultaneously published in the New England Journal of Medicine, showed that among 5,083 study participants:
- Postmenopausal women can safely forgo chemotherapy for endocrine therapy treatment.
- Premenopausal women benefited from sequential chemo- and endocrine therapy.
A symposium debate, "RxPONDER: Was it All Ovarian Suppression?," covered questions that remain about ovarian suppression in premenopausal women, according to Dr. Linden. Chemotherapy can cause early menopause, and only a small fraction of patients in RxPONDER received ovarian suppression. It remains unclear whether suppression due to chemotherapy contributed to the observed results.
“Other investigators presented trials at SABCS, including updates from the SOFT and TEXT trials, comparing various combinations of tamoxifen, ovarian suppression and aromatase inhibitors," she says. "Basically, the data suggests that endocrine therapy — not surprisingly — is important in both premenopausal and postmenopausal women.”
2. Metformin Not Effective for Preventing Recurrence of Early Breast Cancer
Metformin has attracted attention as a possible adjuvant treatment in breast cancer. Preclinical studies showed the diabetes drug reduced Ki67 expression and slowed the growth of breast cancer cells.
But long-awaited results from the latest study presented at SABCS showed that metformin offered no improvement in disease-free survival or overall survival.
“Unfortunately, it’s a negative study, but it’s great that the study was conducted and publicly reported,” says Dr. Linden. “This busts the myth of metformin, which has been out there for a long time and was based on limited data.”
Dr. Linden noted that the study did not include patients taking metformin for their diabetes and does not recommend discontinuation of metformin in these patients.
The Canadian Cancer Trials Group MA.32 trial randomly assigned participants to receive adjuvant metformin or placebo for up to 5 years. They included 3,649 nondiabetic patients with:
- Nonmetastatic HR+ or HR- breast cancer
- Diagnosis within the previous year
- Excision with negative margins
- Moderate or high risk for recurrence after surgery
The MA.32 study did find a benefit with metformin in HER2+ patients with at least one C allele of the rs11212617 single nucleotide polymorphism. This data is in a limited subset, says Dr. Linden, and it is not clear how to put this in the context of modern HER2 therapy, a field which has seen a tremendous amount of improvement using other strategies. More data is needed to determine the significance of metformin in this group.
“The bigger question with HER2+ patients is whether they all need aggressive therapy,” she says. “Some patients may be able to have a little less intense therapy and fewer long-term side effects. At SCCA, we’re trying to determine if less is more in a TBCRC-sponsored trial.”
3. Immunotherapy Effective for Triple Negative Breast Cancer
Though immunotherapy has revolutionized cancer treatment, it’s not widely used in patients with breast cancer. The KEYNOTE-522 trial evaluated neoadjuvant/adjuvant pembrolizumab with and without chemotherapy for high-risk, early-stage, triple negative breast cancer.
The benefit of added pembrolizumab was clear, improving event-free survival significantly. Yet there are drawbacks.
“Immunotherapy has increased the cure rates for triple negative patients,” says Dr. Linden. “But because it can be toxic and increase patients’ risk of developing an autoimmune disease, we are limiting its use to stage 3 patients.”
At SCCA, current studies are looking at immunotherapy for other patients, including those with metastatic, PD-L1 negative, triple negative breast cancer.
4. Antibody Drug Conjugate Trial Results Encouraging
Antibody drug conjugates combine the precision of an antibody with a payload of chemotherapy. Sacituzumab govetecan is an FDA-approved drug in this class for triple negative metastatic breast cancer, and others are emerging rapidly.
“These types of drugs are going to make a big difference for patients. They are chemo-like but appear to be more active and less toxic than standard chemo,” Dr. Linden says.
SABCS showcased several immune conjugates, including:
- Trastuzumab deruxtecan (T-DXd): A DESTINY trial update showed T-DXd, a TROP2-specific antibody drug conjugate, is superior to TDM-1 for HER2+ patients as a second line treatment.
- Datopotamab deruxtecan (Dato-DXd): Dato-DXd, which also targets TROP2, was recently approved by the FDA. In preliminary results from the phase 1 TROPION-PanTumor01 study, Dato-DXd showed promising anti-tumor activity and a manageable safety profile in patients with previously treated triple negative breast cancer.
- Patritumab deruxtecan (HER3-DXd): Trial results showed this HER3-directed antibody drug conjugate is a promising therapeutic for all tumor types.
Dr. Linden says that TROP2 is clearly a robust target and HER3 may follow suit. An exciting new clinical trial led by SCCA researchers will look more closely at patritumab deruxtecan.
5. Oral SERDs Show Promise for Treating ER+ Metastatic Breast Cancer
The first line of treatment for patients with ER+ metastatic breast cancer is an aromatase inhibitor (AI) plus a CDK 4/6 inhibitor. However, most patients eventually develop resistance.
The EMERALD trial looked at a new oral SERD, elacestrant, as second line therapy. Some patients in the control group received fulvestrant while some got an AI. Results found that elacestrant improved disease control significantly.
“Oral SERDs are clearly a new advance for patients with ER+ metastatic breast cancer,” Dr. Linden says. “The drugs are well tolerated and appealing as an oral medication. They also appear to be more effective.”
SCCA is participating in clinical trials of three new oral SERDS. “It’s wonderful to have alternatives to continuous chemotherapy for patients,” Dr. Linden says.
At the same time, she says it was "stunning" that more than half the patients came off the EMERALD study in the first two months for progression, the majority for visceral metastases.
"It makes us wonder whether partnering elacestrant with a different molecularly targeted agent would have improved the outcome," Dr. Linden says. "This finding also leaves us in the dark about SERD use in the more common type of patient who develops bone and soft tissue metastases (not visceral metastases)."
She adds, "One of the problems we face in metastatic cancer is how to include a diverse group of patients in our studies. Our work in estrogen receptor imaging using FES PET is helping address this challenge.”
6. FES- and FDG-PET Imaging Helps Researchers understand ER+ tumors in bone
SCCA researchers helped develop FES, an estrogen receptor-targeted tracer. Using PET imaging, FES detects ER expression in patients with ER+ metastatic breast cancer. It also shows whether a SERD blocks the uptake of estrogen to the tumor.
Dr. Linden and Dr. Jennifer Specht, SCCA physician and Professor of Oncology at the University of Washington School of Medicine, presented their research on FES- and FDG-PET imaging at a SABCS spotlight session.
“These tools are important because they can help us recommend different therapies for patients, including the multiple SERDs we are currently studying,” says Dr. Linden.
Dr. Linden and Dr. Specht are each leading national cooperative studies with ECOG ACRIN to assess different applications of FES-PET (EAI142) and FDG-PET (EA1183).
Breast cancer care at SCCA
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