An overall survival benefit has now emerged for sacituzumab govitecan-hziy in patients with previously treated hormone receptor–positive/HER2-negative locally recurrent inoperable or metastatic breast cancer, according to a planned second interim analysis of the phase III TROPiCS-02 trial. These findings were presented by Hope S. Rugo, MD, FASCO, at the European Society for Medical Oncology (ESMO) Congress 2022 (Abstract LBA76). The drug is the first TROP2–directed antibody-drug conjugate to demonstrate a significant improvement in overall survival in this subset of breast cancer.
Hope S. Rugo, MD, FASCO
“Sacituzumab govitecan resulted in a median 3.2-month improvement in survival, representing a 21% relative reduction in the risk of death. The overall survival benefit was consistent across predefined subgroups, including patients with at least three prior chemotherapy regimens in the metastatic setting, visceral metastases, and prior endocrine therapy in the metastatic setting for at least 6 months,” said Dr. Rugo, 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.
“TROPiCS-02 is the largest late-line trial specifically conducted in the hormone receptor–positive/HER2-negative 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 the study’s invited discussant Meritxell Bellet Ezquerra, MD, PhD, a senior researcher at the Vall d'Hebron Institute of Oncology in Barcelona.
Sacituzumab govitecan, an anti-TROP2 antibody-drug conjugate, is approved by the U.S. Food and Drug Administration for patients with metastatic triple-negative breast cancer after at least two prior treatments (one or more for metastatic disease). The findings from TROPiCS-02 suggest the drug can be useful in women with hormone receptor–positive tumors as well.
Overall Survival Analysis
Dr. Rugo presented the results of the planned second interim analysis of overall survival based on the occurrence of 390 events at a data cutoff of July 1, 2022. After a median follow-up of 12.6 months, the median overall survival difference, which was not statistically significant in the previous analysis, has now widened to 14.4 months for patients who received sacituzumab govitecan vs 11.2 months for those treated with chemotherapy (hazard ratio [HR] = 0.79, P = .020).
In addition, patients receiving sacituzumab govitecan had improvements in response, duration of response, and overall health-related quality of life. They also had a delay in deterioration of fatigue and global health status quality of life.
“The statistically significant and clinically meaningful benefit of sacituzumab govitecan over treatment by physician’s choice from the TROPiCS-02 study supports the use of sacituzumab as a novel therapy for patients with pretreated endocrine-resistant hormone receptor–positive, HER2-negative metastatic breast cancer,” Dr. Rugo said.
About TROPiCS-02
TROPiCS-02 is a global, multicenter, open-label, phase III study that randomly assigned 543 patients to sacituzumab govitecan (10 mg/kg on days 1 and 8 every 21 days) vs physicians’ choice of chemotherapy (eribulin, capecitabine, gemcitabine, or vinorelbine). Patients had received two to four prior lines of therapy (median of three), including endocrine therapy and inhibitors of cyclin D kinases 4 and 6 (CDK4/6).
The primary endpoint is progression-free survival by blinded independent central review. Secondary endpoints include overall survival, overall response rate, clinical benefit rate, duration of response, safety, tolerability, and quality of life. In the study, HER2 negativity was defined immunohistochemistry score of 0, 1+, or 2+ with a negative in situ hybridization test.
KEY POINTS
- After a median follow-up of 12.6 months, the median overall survival difference, which was not statistically significant in the previous analysis, has now widened to 14.4 months for patients who received sacituzumab govitecan vs 11.2 months for those treated with chemotherapy.
- In addition, patients receiving sacituzumab govitecan had improvements in response, duration of response, and overall health-related quality of life. They also had a delay in deterioration of fatigue and global health status quality of life.
The primary progression-free survival analysis of TROPiCS-02 and the first of three planned overall survival analyses was presented by Dr. Rugo and colleagues at the 2022 ASCO Annual Meeting (Abstract LBA1001). Meeting the primary endpoint, the study showed a statistically significant improvement in progression-free survival by independent review based on median progression-free survival of 5.5 months in the sacituzumab govitecan arm and 4.0 months in the chemotherapy arm (HR = 0.66, P = .0003). Overall survival data were immature, but a numerical trend for improvement was seen, with median overall survival of 13.9 months vs 12.3 months (HR = 0.84, P = .14), respectively.
Safety Profile
The safety profile for sacituzumab govitecan was consistent with prior studies, and no new safety signals emerged in this patient population.
Gilead Sciences has submitted a supplemental biologics license application to the FDA.
Disclosure: Dr. Rugo reported consulting/advisory roles with Samsung, Puma, NAPO and Blueprint and institutional research funding from multiple companies. Dr. Bellet Ezquerra reported relationships with Pfizer, Novartis, and Lilly, and is a member of the SOLTI Executive Board and Scientific Committee. For full disclosures of the study authors, visit oncologypro.esmo.org.
