The use of sacituzumab govitecan (Trodelvy) an antibody-drug conjugate, resulted in longer progression-free survival compared to physician’s choice of chemotherapy in patients who have received many prior therapies and who had hormone-receptor positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer, according to new research to be presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.
HR+/HER2- 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.
Trial results showed that use of sacituzumab govitecan, where more than 50% of patients had received three or more lines of chemotherapy, resulted in improved median PFS compared to standard chemotherapy (5.5 vs. 4.0 months); PFS 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 OS (13.9 vs. 12.3 months) in the first of three planned OS 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 median duration of response was 7.4 vs. 5.6 months, respectively.
Overall, 74% vs. 60% of patients (sacituzumab govitecan vs. 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 Hope S. Rugo, MD, FASCO, lead author, who is a 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.”
In the United States (U.S.), 5% to 10% of breast cancers are classified as aggressive and high risk. In 2022, invasive breast cancer will be newly diagnosed in an estimated 287,850 women and 2,710 men.
Almost one in three cases of early-stage breast cancer eventually become metastatic, and among patients with HR+/HER2- metastatic disease, the five-year relative survival rate is 30%.
Treatment for HR+/HER2- 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.
Sacituzumab govitecan is an antibody-drug conjugate, which means it consists of a protein (in this case a Trop-2-directed antibody) joined to an anti-cancer drug that is uniquely delivered to cells that express the antibody target.
The Trop-2 protein is a cell surface antigen highly expressed in several different kinds of cancer, including more than 90% of breast and bladder cancers. Sacituzumab govitecan is approved for metastatic triple-negative breast cancer previously treated with two or more prior therapies (at least one in the metastatic setting).
If sacituzumab govitecan is approved by the U.S. Food and Drug Administration to treat HR+/HER2- advanced breast cancer, it would be the first antibody-drug conjugate approved for use in this setting.
The TROPiCs-02 phase III clinical trial randomly assigned patients at 113 international locations with HR+/HER2- 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 PFS with a secondary endpoint of OS.
The patients in the study continue to be followed for OS 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 tumour types and earlier lines of therapy.
TROPiCS-02 is an industry trial being sponsored by Gilead Sciences, Inc.
“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 HR+/HER2- 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.
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