Updated results from the phase 3 TROPiCS-02 trial show that sacituzumab govitecan (Trodelvy) demonstrated a statistically significant improvement in overall survival (OS) of 3.2 months in endocrine therapy-resistant HR+/HER2- metastatic breast cancer when compared to a physician’s choice of chemotherapy. The findings were presented today at the European Society for Medical Oncology (ESMO) Congress 2022 in Paris (Abstract LBA76).
“[TROPiCS-02] is the largest late-line trial specifically conducted in the ER+/HER2- metastatic breast cancer population and addresses a real unmet medical need. Altogether, the results in my opinion are clinically meaningful and should lead to regulatory approval,” said Meritxell Bellet Ezquerra, MD, PhD, a senior researcher at the Vall d'Hebron Institute of Oncology in Barcelona, Spain, and a discussant at the ESMO session where the results were presented. The study was funded by Gilead Sciences.
Sacituzumab govitecan is an antibody-drug conjugate that is approved by the U.S. Food and Drug Administration for treating metastatic triple-negative breast cancer in patients who have received two or more prior systemic therapies. The TROPiCs-02 trial randomized 272 HR+/HER2- metastatic breast cancer patients to receive sacituzumab govitecan, while 271 were given physician’s choice of chemotherapy. Each patient had been treated with endocrine therapy, CDK4/6 inhibition, and two to four chemotherapy regimens.
Initial findings presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting showed that patients who received sacituzumab govitecan had a median progression-free survival (PFS) of 5.5 months compared with 4.0 months in the chemotherapy arm, while median OS was 13.9 months compared with 12.3 months. This OS difference was not statistically significant.
The updated results presented at ESMO had a data cutoff of July 1, 2022, and showed that the median OS gap had widened to 14.4 months for patients who received sacituzumab govitecan and 11.2 for those given chemotherapy. In addition, the objective response rate was 21% in the sacituzumab govitecan arm and 14% in the chemotherapy one.
“The safety profile was manageable and consistent with that reported in previous studies, and no new safety signals were identified,” said Hope Rugo, MD, lead author of the study and professor of medicine and director of Breast Oncology and Clinical Trials Education at the University of California San Francisco Helen Diller Family Comprehensive Cancer Center.
One remaining question raised by the study is whether and how sacituzumab govitecan should be sequenced with trastuzumab deruxtecan (Enhertu), a HER2-targeting antibody-drug conjugate. Results presented at the 2022 ASCO Annual Meeting showed that trastuzumab deruxtecan improved OS by more than six months in patients with HER2-low, HR+ metastatic breast cancer. Both Dr. Rugo and Dr. Bellet Ezquerra said sequential therapy should be explored, as the therapies have different toxins and antibodies.
“I think sequential therapy should be studied, and it is a treatment option for our patients as well,” said Dr. Rugo.
TROPiCS-02 was funded by Gilead Sciences.
Dr. Rugo reported relationships with several companies, including AstraZeneca, Gilead Sciences, and Ayala Pharmaceuticals.
Dr. Bellet Ezquerra reported relationships with Pfizer, Novartis, and Lilly and is a member of the SOLTI Executive Board and Scientific Committee.