Trodelvy Produces Significant Improvement in Progression-Free Survival in HR+/HER2- Metastatic Breast Cancer

Treatment with sacituzumab govitecan-hziy (Trodelvy; Gilead Sciences) produced a statistically significant and clinically meaningful 34% decrease in the risk of disease progression or death in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer. Results of the phase 3 TROPiCS-02 study were presented during an oral session (Abstract #LBA1001) at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

Sacituzumab govitecan-hziy achieved the primary endpoint of improved progression-free survival (PFS) in TROPiCS-02 (median PFS 5.5 vs. 4 months; HR: 0.66; 95% CI: 0.53-0.83; P<0.0003) compared with physicians’ choice of chemotherapy (TPC; [eribulin, capecitabine, gemcitabine, or vinorelbine]) in 543 heavily pre-treated patients with HR+/HER2- metastatic breast cancer previously administered endocrine therapy, CDK4/6 inhibitors, and 2 to 4 lines of chemotherapy. At the first interim analysis, the investigators noted a demonstrated trend in improved overall survival (OS), which was the study’s key secondary endpoint; however, they noted these data are immature and patients will be followed for a subsequent OS analysis.

“For patients with HR+/HER2- metastatic breast cancer, resistance to endocrine therapy is inevitable in almost all cases. The standard of care is then limited to sequential single agent chemotherapy, with declining response rates, disease control and quality of life,” Hope Rugo, MD, FASCO, professor of Medicine and director, Breast Oncology and Clinical Trials Education at the University of California San Francisco Comprehensive Cancer Center, said in a press release. “In TROPiCS-02, we enrolled heavily pre-treated patients with metastatic breast cancer who had disease progression following multiple lines of chemotherapy. To observe a clinically meaningful reduction in the risk of disease progression or death in these patients with limited treatment options is remarkable. Sacituzumab govitecan-hziy will be an important potential future treatment option for these patients.”

At 1 year, the findings showed that 3 times as many patients administered sacituzumab govitecan-hziy were progression-free versus patients administered TPC (21% versus 7%). Improved PFS from treatment with sacituzumab govitecan-hziy was found to be consistent across key patient subgroups, including those previously administered 3 or more chemotherapy regimens for metastatic disease (HR: 0.70; CI: 0.52-0.95), patients with visceral metastasis (HR: 0.66; CI: 0.53-0.83), and those 65 years of age and older (HR: 0.59; CI: 0.38-0.93).

One of the study’s secondary endpoints, a prespecified quality of life (QoL) analysis using the EORTC QLQ-C30 instrument, also favored sacituzumab govitecan-hziy versus TPC in demonstrating a meaningful benefit. In the evaluable patient population, the investigators noted improved global health status and fatigue with sacituzumab govitecan-hziy (n=234) versus patients administered TPC (n=207).

The safety profile for sacituzumab govitecan-hziy was consistent with previous trials and there were no new concerns identified. The most frequent grade ≥3 treatment-related adverse events for sacituzumab govitecan-hziy versus TPC were neutropenia (51% versus 38%), diarrhea (9% versus 1%), leukopenia (9% versus 5%), anemia (6% versus 3%), fatigue (6% versus 2%) and febrile neutropenia (5% versus 4%).

Sacituzumab govitecan-hziy is a conjugated Trop-2-directed antibody and topoisomerase inhibitor that was previously approved for the treatment of patients with triple-negative breast cancer administered 2 prior therapies at minimum for metastatic disease. The FDA also granted accelerated approval to sacituzumab govitecan-hziy in April 2021 based on duration and level of tumor response for the treatment of patients with locally advanced or metastatic urothelial cancer who previously received a platinum-containing chemotherapy and either a programmed cell death protein 1 or programmed death-ligand 1 inhibitor.

“With Trodelvy, our bold ambition is that it will help transform care for people living with cancer, including in pre-treated HR+/HER2- metastatic breast cancer, where more options are needed,” Bill Grossman, MD, PhD, senior vice president, Therapeutic Area Head, Gilead Oncology, said in a press release. “We look forward to continuing discussions with regulatory agencies to further understand how Trodelvy can impact this patient population with a high unmet need.”

Reference

Trodelvy® Improved Progression-Free Survival by 34% in Heavily Pre-Treated HR+/HER2- Metastatic Breast Cancer Patients. Gilead Sciences. News release. June 5, 2022. https://www.gilead.com/news-and-press/press-room/press-releases/2022/6/trodelvy-improved-progressionfree-survival-by-34-in-heavily-pretreated-hrher2-metastatic-breast-cancer-patients