Sacituzumab Govitecan Prolongs PFS in HR+/HER- Metastatic Breast Cancer

Hope Rugo, MD

A statistically significant improvement in progression-free survival (PFS) was demonstrated with sacituzumab govitecan-hziy (Trodelvy) versus physician’s choice of chemotherapy in patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (mBC) who received prior endocrine therapy, CDK4/6 inhibitors, and 2 to 4 lines of chemotherapy, meeting the primary end point of the phase 3 TROPiCS-02 study (NCT03901339).¹

A 30% reduction in the risk of disease progression or death was achieved with sacituzumab govitecan compared with chemotherapy. These findings were consistent with those previously observed in the phase 1/2 IMMU-132-01 study of sacituzumab govitecan in patients with epithelial cancer (NCT01631552). Prior interim analysis results also showed an improvement in overall survival (OS) with sacituzumab govitecan versus chemotherapy, meeting a secondary end point of the TROPiCS-02 trial.

“HR+/HER2- breast cancer accounts for approximately 70% of all breast cancer cases. Patients with advanced breast cancer may eventually develop endocrine resistance, then resistance to a limited set of sequential chemotherapy options,” said Hope Rugo, MD, professor of medicine and director, breast oncology and clinical trials education at the University of California San Francisco Comprehensive Cancer Center, in a press release. “These data show the potential for Trodelvy to address an important unmet need for patients with HR-positive/HER2-negative metastatic breast cancer who have been heavily pretreated.”

In TROPiCS-02, patients received sacituzumab govitecan 10 mg/kg by intravenous (IV) injection on days 1 and 8 of a 21-day cycle. In the physician’s choice chemotherapy arm, patients received either eribulin, capecitabine, gemcitabine, or vinorelbine. Eribulin is administered at 1.4 mg/m² for patient treated at North American sites or 1.23 mg/m² for patients at European sites on day 1 and 8 of a 21-day cycle.²

Patients treated with capecitabine receive 1000-1250 mg/m² of the agent orally twice daily for 2 weeks followed by a 1-week rest period during a 21-day cycle. Gemcitabine is administered at 800-1200 mg/m² via IV on days 1, 8, and 15 of each 28-day cycle, and vinorelbine is administered at 5 mg/m² via IV on day 1 weekly cycle per institution.

In addition to PFS and OS, the study is also assessing objective response rate, duration of response, clinical benefit rate, time to deterioration, quality of life, and the percentage of patients with adverse events (AEs), serious AEs, and clinically significant laboratory abnormalities.

To be eligible for the study, patients must be 18 year of age or older with documented evidence of HR-positive, HER2-negative mBC that is refractory to or relapsed after at least 2, and no more than 4, prior systemic chemotherapy regimens. Patients must be eligible for 1 of chemotherapy options in the physician’s choice arm, have documented disease progression after the most recent therapy, and have adequate bone marrow, renal, and hepatic function.

The study excludes patients who received previous treatment with topoisomerase 1 Inhibitors, or those with medical conditions that may impact the effectiveness or safety of study treatment.

The study is ongoing at 113 locations in the United States, Canada, and Europe. Full results from the TROPiCS-02 analysis will be presented during an upcoming medical meeting.

“Trodelvy demonstrated consistent activity in this difficult-to-treat patient population,” said Merdad Parsey, MD, PhD, chief medical officer, Gilead Sciences, in the press release.1 “We are evaluating the data and will explore potential pathways with regulatory authorities to bring Trodelvy to this group of patients. As we work to expand the patient benefit of Trodelvy beyond its current indications for second-line metastatic triple-negative breast cancer and accelerated approval in second-line metastatic bladder cancer, we are pursuing studies across multiple tumor types and earlier lines of therapy.”

_References:

_{1. Phase 3 TROPiCS-02 study met the primary endpoint of progression-free survival in late-Line HR+/HER2- metastatic breast cancer. News release. Gilead Sciences, Inc. March 7, 2022. Accessed March 8, 2022. https://bit.ly/3IZ4P72}

_{2. Study of sacituzumab govitecan-hziy versus treatment of physician's choice in participants with HR+/HER2- metastatic breast cancer (TROPiCS-02). Clinicaltrials.gov. Accessed March 8, 2022. https://bit.ly/3IUeewx}