At the 2022 American Society of Clinical Oncology (ASCO®) Annual Meeting held in Chicago, Illinois, this year’s theme was Advancing Equitable Cancer Care Through Innovation. The program featured more than 200 sessions and 2500 poster presentations on a vast array of topics in cancer care.
Adam M Brufsky, MD, PhD, FACP, is among the many clinician scientists who presented results of research on metastatic breast cancer. Dr Brufsky is a professor of medicine and associate chief for the division of hematology/oncology at the University of Pittsburgh School of Medicine, codirector of the Comprehensive Breast Cancer Center at the University of Pittsburgh Medical Center, and medical director of the Magee-Women’s Cancer Program at the UPMC Hillman Cancer Center in Pittsburgh, Pennsylvania.
Among the wide range of research findings presented at the 2022 ASCO conference on the treatment of metastatic breast cancer, which stood out to you and why?
Results of the DESTINY-Breast04 study (ClinicalTrials.gov Identifier: NCT03734029) were the most significant findings presented this year in terms of management of metastatic breast cancer.1 In this randomized, open-label phase 3 trial of 557 patients with human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer, median progression-free survival (PFS) and overall survival (OS) were 9.9 months and 23.4 months, respectively, in patients who were assigned to trastuzumab deruxtecan. For patients who were assigned to receive the physician’s choice of treatment, the median PFS was 5.1 months and median OS was 16.8 months.
The use of an effective antibody-drug conjugate with an OS benefit in progressive estrogen receptor-positive metastatic breast cancer is a major advance. This drug seems to work not only in HER2-low breast cancers but also in other cancers with HER2 expression, such as biliary tract cancer, non-small-cell lung cancer, colorectal cancer, and endometrial cancer.2
Your study examining the role of socioeconomic status in metastatic breast cancer survival reported worse survival among patients with low socioeconomic status.3 What are the implications of these findings and what is the significance of the observation that race was no longer a predictor of worse survival when socioeconomic status was considered?
In our analysis, race is a surrogate of socioeconomic status. If these data are replicated, it would indicate that we should be investing in breast cancer care in areas of low socioeconomic status. Individuals with low socioeconomic status are less likely to utilize health care services owing to copays, expensive travel, and the cost of missing work. These are obstacles that our health care system could address to improve patients’ access to breast cancer treatment.
You also coauthored a study (ClinicalTrials.gov Identifier: NCT01953926) of combination therapy with neratinib plus fulvestrant plus trastuzumab for hormone receptor (HR)-positive, HER2-negative, HER2-mutant metastatic breast cancer.4 What were the key findings, including biomarker and safety analyses?
We found that the neratinib plus fulvestrant plus trastuzumab combination has activity in patients with advanced breast cancer and an activating HER2 mutation on further follow-up. The biomarker response is the mutation in the HER2 molecule. It is interesting to note that this triple-agent combination had activity across the spectrum of HER2 mutations. Diarrhea was the major side effect noted in our safety analyses.
Many studies of potential therapies for metastatic breast cancer that were presented at ASCO also included biomarker analyses. What findings struck you as most significant? What is the ultimate goal regarding biomarker use in the treatment of metastatic breast cancer?
The ultimate goal of biomarker investigation is to determine, prior to initiation of therapy with a specific agent, the potential activity of the agent in an individual patient and the prognosis of that patient. This approach serves to identify subgroups of patients who are more likely to benefit from a particular treatment. For example, in the SOLAR-1 phase 3 trial (ClinicalTrials.gov Identifier: NCT02437318) of alpelisib plus fulvestrant for patients with PIK3CA-mutated, HR-positive, HER2-positive advanced breast cancer, it is interesting that there was benefit even in patients with markers of treatment resistance such as fibroblast growth factor receptor 1 (FGFR1).5
In another study presented at the conference, there was a 7-gene predictive biomarker signature for ductal carcinoma in situ for a low-risk group who perhaps did not require radiation therapy to prevent breast recurrence.6
Another study presented at the 2022 ASCO conference found superior survival among patients with previously treated metastatic triple-negative breast cancer (TNBC) following treatment with sacituzumab govitecan compared with single-agent chemotherapy.7 What are current treatment recommendations regarding this drug?
This study extends the results of the ASCENT trial (ClinicalTrials.gov Identifier: NCT02574455), showing yet another subgroup of patients with TNBC has experienced substantially improved OS on sacituzumab. Sacituzumab govitecan is an antibody-drug conjugate that has a payload called SN-38, a potent active metabolite of irinotecan, so it goes directly to the cancer cells and delivers the payload. Sacituzumab govitecan is indicated for second- and third-line treatment of metastatic TNBC.
Various studies on metastatic breast cancer presented this year have focused on or mentioned hyperglycemia as a side effect of certain therapies.8 What is the significance of hypoglycemia in the management of metastatic breast cancer and how does it affect disease outcomes?
Hyperglycemia per se does not affect outcomes of metastatic breast cancer but it can limit the use of certain agents such as phosphoinositide 3-kinase (PI3K) inhibitors like alpelisib, for which hyperglycemia is the major side effect. Basically, insulin needs the PI3K pathway to activate glucose uptake. Inhibition of the PI3K pathway inhibits insulin from driving glucose into the cells. Therefore, glycemic control is important in metastatic breast cancer therapy.
What additional questions would you like to see investigated regarding the treatment of metastatic breast cancer?
I think we are just beginning to understand and utilize manipulation of the immune system in the treatment of breast cancer. Early research suggests that immune checkpoint inhibitors may have some activity in preoperative chemotherapy.9 There are also many other immune manipulators on the horizon with potential activity in breast cancer.10
Key Takeaways
- Antibody-drug conjugates for the treatment of HER2-positive metastatic breast cancer represent a major advance that may also benefit patients with other cancers that express HER2.
- Research suggests the need for health care systems to invest in areas of low socioeconomic status to improve breast cancer treatment outcomes through better access to care.
- Besides immune checkpoint inhibitors, many other emerging immune manipulators may play a role in the treatment of metastatic breast cancer
This Q&A was edited for clarity and length.
Disclosure
Adam M Brufsky, MD, PhD, FACP, reported relationships with AbbVie Inc; Agendia, Inc.; Bayer HealthCare Pharmaceuticals Inc; Biotheranostics, Inc.; Coherus BioSciences, Inc.; Daiichi Sankyo Company Limited/Eli Lilly and Company; Eisai Inc.; Eli Lilly and Company; Genentech, Inc.; Gilead Sciences Inc; Immunomedics, Inc.; Merck & Co Inc; Myriad Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Pfizer Inc; Puma Biotechnology, Inc.; Seagen Inc; Genetics; and Tyme Technologies Inc.
References
1. Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): results of DESTINY-Breast04, a randomized, phase 3 study. Abstract presented at: 2022 American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2022; Chicago, IL. Abstract LBA3.
2. Tsurutani J, Iwata H, Krop I, et al. Targeting HER2 with trastuzumab deruxtecan: a dose-expansion, phase I study in multiple advanced solid tumors. Cancer Discov. 2020;10(5):688-701. doi:10.1158/2159-8290.CD-19-1014
3. Narayanan SP, Rosenzweig MQ, Ren D, Oesterreich S, Lee AV, Brufsky A. Effect of socioeconomic status as measured by Neighborhood Deprivation Index on survival in metastatic breast cancer. Abstract presented at: 2022 American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2022; Chicago, IL. Abstract 1013.
4. Jhaveri KL, Goldman JW, Hurvitz SA, et al. Neratinib plus fulvestrant plus trastuzumab (N+F+T) for hormone receptor-positive (HR+), HER2-negative, HER2-mutant metastatic breast cancer (MBC): outcomes and biomarker analysis from the SUMMIT trial. Abstract presented at: 2022 American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2022; Chicago, IL. Abstract 1028.
5. Juric D, Rugo HS, Reising A, et al. Alpelisib (ALP) + fulvestrant (FUL) in patients (pts) with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2−) advanced breast cancer (ABC): biomarker (BM) analyses by next-generation sequencing (NGS) from the SOLAR-1 study Abstract presented at: 2022 American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2022; Chicago, IL. Abstract 1006.
6. Whitworth PW, Shah CS, Vicini FA, et al. Assessing the benefit of adjuvant endocrine therapy in patients following breast-conserving surgery with or without radiation stratified by a 7-gene predictive DCIS biosignature. Abstract presented at: 2022 American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2022; Chicago, IL. Abstract 502.
7. Bardia A, Tolaney SM, Loirat D, et al. Sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) in patients (pts) with previously treated, metastatic triple-negative breast cancer (mTNBC): final results from the phase 3 ASCENT study. Abstract presented at: 2022 American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2022; Chicago, IL. Abstract 1071.
8. Ge X, Behrendt CE, Yost SE, et al. Predicting hyperglycemia among patients receiving alpelisib plus fulvestrant for metastatic breast cancer. Abstract presented at: 2022 American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2022; Chicago, IL. Abstract 1060.
9. Xin Y, Shen G, Zheng Y, et al. Immune checkpoint inhibitors plus neoadjuvant chemotherapy in early triple-negative breast cancer: a systematic review and meta-analysis. BMC Cancer. 2021;21(1):1261. doi:10.1186/s12885-021-08997-w
10. Tabana Y, Okoye IS, Siraki A, Elahi S, Barakat KH. Tackling immune targets for breast cancer: beyond PD-1/PD-L1 axis. Front Oncol. 2021;11:628138. doi:10.3389/fonc.2021.628138
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Reviewed June 2022
