Hope Rugo, MD
Treatment with the antibody-drug conjugate sacituzumab govitecan-hziy resulted in longer progression-free survival compared to physician’s choice of chemotherapy in patients who have received many prior therapies for hormone receptor–positive/HER2-negative metastatic breast cancer, according to research presented today by Hope Rugo, MD, and colleagues, at the 2022 ASCO Annual Meeting (Abstract LBA1001).
Hormone receptor–positive/HER2-negative breast cancer is the most common subtype of advanced breast cancer and the most common cancer in women worldwide, accounting for approximately 70% of all breast cancer cases. Among patients with hormone receptor–positive/HER2-negative metastatic disease, the 5-year relative survival rate is 30%. Treatment for hormone receptor–positive/HER2-negative metastatic breast cancer initially includes sequential endocrine therapy combined with targeted agents, and as the disease becomes resistant to endocrine-based therapy, treatment is limited to sequential single-agent chemotherapy with increasingly shorter durations of benefit. For patients treated with single-agent chemotherapy, the prognosis remains poor.
“This trial shows that sacituzumab govitecan, which is already approved for the treatment of metastatic triple-negative breast cancer, may represent an important new option for patients with endocrine-resistant hormone receptor–positive/HER2-negative metastatic breast cancer. This would address a critical unmet medical need, given the limited number of effective treatment options currently available for these patients,” said Jane Lowe Meisel, MD, ASCO Expert in breast cancers.
Study Details
The TROPiCs-02 phase III clinical trial randomly assigned patients at 113 international locations with hormone receptor–positive/HER2-negative unresectable locally advanced or metastatic breast cancer who had received two to four prior chemotherapy regimens for advanced disease to be given either sacituzumab govitecan or standard chemotherapy (capecitabine, eribulin, vinorelbine, or gemcitabine) until the disease progressed or the toxicity of the drugs became unacceptable. The primary endpoint was progression-free survival, with a secondary endpoint of overall survival.
Trial results showed that the use of sacituzumab govitecan, where more than 50% of patients had received three or more lines of chemotherapy, resulted in improved median progression-free survival compared to standard chemotherapy (5.5 vs 4.0 months); progression-free survival rates at 6 and 12 months were 46% vs 30% and 21% vs 7%, respectively. Sacituzumab govitecan vs standard chemotherapy showed a nonsignificant trend for improvement in overall survival (13.9 vs 12.3 months) in the first of three planned overall survival analyses, with follow-up ongoing. The overall response rate (21% vs 14%) and clinical benefit rate (34% vs 22%) were higher with sacituzumab govitecan vs standard therapy, and the median duration of response was 7.4 vs 5.6 months, respectively.
Overall, 74% of patients receiving sacituzumab govitecan vs 60% of those receiving standard chemotherapy had adverse events, including low white blood cell counts (51% vs 39%) and diarrhea (10% vs 1%). Adverse events leading to discontinuation of sacituzumab govitecan vs standard chemotherapy were low (6% vs 4%).
“It is very gratifying to see the benefit of sacituzumab govitecan for these patients who have had very limited treatment options,” said Dr. Rugo, who is Professor of Medicine and Director of Breast Oncology and Clinical Trials Education at the University of California San Francisco Comprehensive Cancer Center. “Longer follow-up is needed to determine the impact on overall survival, and additional prespecified analyses will help us understand the potential role of sacituzumab govitecan in a setting where there are currently no other targeted treatment options available.”
Next Steps
The patients in the study continue to be followed for overall survival and long-term safety endpoints. Researchers are working to expand the patient benefit of sacituzumab govitecan beyond its current indications for second-line metastatic triple-negative breast cancer and accelerated approval in second-line metastatic bladder cancer. They are pursuing studies across multiple tumor types and earlier lines of therapy.
Disclosure: This trial was sponsored by Gilead Sciences, Inc. For full disclosure of the study authors, visit coi.asco.org.
