CHICAGO -- An antibody drug conjugate that targets a cell-surface antigen found on most breast and bladder cancers demonstrated improved progression-free survival over standard chemotherapy in patients with endocrine-resistant hormone receptor positive/HER2 negative metastatic breast cancer.
The agent, called sacituzumab govitecan (Trodelvy, Gilead), was approved on an accelerated basis in 2020 by the Food and Drug Administration for patients with unresectable locally advanced or metastatic triple-negative breast cancer. It received regular approval in 2021.
The conjugate includes an antibody that targets the Trop-2 protein. The antibody is bound to govitecan, which is the active metabolite of the topoisomerase inhibitor 1 irinotecan.
“Sacituzumab demonstrated significant and clinically meaningful benefit, compared with chemotherapy in patients with heavily pretreated endocrine resistant hormone receptor positive, HER2 negative, advanced breast cancer and should be considered a potential treatment in this heavily pretreated patient population,” said lead author Hope S. Rugo, MD, during a press conference held June 4 in Chicago at the annual meeting of the American Society of Clinical Oncology. Dr. Rugo is director of Breast Oncology and Clinical Trials Education at the University of California, San Francisco comprehensive cancer center.
The results drew praise from ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, since patients with HR+/HER2- metastatic breast cancer who become resistant to endocrine therapy are left with only sequential, single-agent chemotherapy. “We’ve all been eagerly awaiting the results of this trial. These estrogen positive endocrine negative resistant patients really are an area of great unmet clinical need, and their cancers can be very difficult to treat,” Dr. Meisel said during the press conference.
Approximately, 74% of all breast cancers are HR positive/HER2 negative. And, of these, 92% of patients live beyond five years, according to the American Cancer Society.
The study found a relatively small 1.5 months difference in median progression-free survival, but the results are nevertheless clinically important, especially given that 21% of patients were progression-free at one year, compared with 7% in the chemotherapy arm. “When you look at the patients who do respond on sacituzumab govitecan, it seems that they tend to respond better and longer. The idea that someone with such heavily pretreated disease could walk into your clinic and you could offer them an option that would allow them a one in five chance of still not having progressed at one year is really huge from a clinical standpoint,” Dr. Meisel said.
“This is what we need, incremental options that may be different or better than chemotherapy, so I think this really represents a step forward for the field,” he said.
Two other antibody-drug conjugates that are FDA approved for HER2-positive breast cancer include ado-trastuzumab emtansine (Kadcyla, Genentech) and fam-trastuzumab deruxtecan (Enhertu, AstraZeneca, and Daiichi Sankyo). This new wave of therapies is exciting, according to Julie Gralow, MD, who is chief medical officer and executive vice president of ASCO. “I think this way of delivering chemotherapy inside the cancer cell by having an antibody directed to something on the cell surface and then internalization is really, really very interesting,” Dr. Gralow said during the press conference.
The study included 543 patients from 113 international centers who had previously received endocrine therapy, CDK4/6 inhibitors, and at least two previous regimens of chemotherapy. Median progression-free survival (PFS) was 5.5 months in the sacituzumab govitecan group and 4.0 months in the chemotherapy group (hazard ratio, 0.66; P <.001). PFS was more frequent at 6 months (46% vs. 30%) and 12 months (21% vs. 7%). There was no significant improvement in overall survival (13.9 months vs. 12.3 months). The sacituzumab govitecan group had higher rates of overall response (21% vs. 14%) and clinical benefit (34% vs. 22%), as well as a longer median duration of response (7.4 vs. 5.6 months).
Adverse events were more common with sacituzumab govitecan (74% vs. 60%), including low white blood cell counts (51% vs. 39%) and diarrhea (10% vs. 1%). Both groups had low rates of treatment discontinuation due to adverse events (6% in sacituzumab govitecan vs. 4% in chemotherapy).
Dr. Rugo has received honoraria from Puma Biotechnology and Samsung Bioepis, has consulted for Napo Pharmaceuticals, and has received funding from Astellas Pharma, AstraZeneca, Ayala Pharmaceuticals, Daiichi Sankyo, Genentech, Gilead Sciences, Lilly, Merck, Novartis, OBI Pharma, Odonate Therapeutics, Pfizer, and Sermonix Pharmaceuticals. Dr. Meisel has advised or consulted for Medscape and Total Health Conferencing. She has advised or consulted for AstraZeneca, Curio Science, Genentech, GlaxoSmithKline, Novartis, and SeaGen. She has received research funding from Pfizer and Seattle Genetics. She has received travel, accommodation, or expenses from Pfizer, Puma Biotechnology, and Total Health Conferencing.