FDA Grants Priority Review for Trodelvy in HR+/HER2- Metastatic Breast Cancer Following Positive Survival Data
Key Insights
The FDA has accepted Gilead's supplemental biologics license application for Trodelvy in pre-treated HR+/HER2- metastatic breast cancer (search) patients, granting priority review with a target action date of February 2023.
The Phase 3 TROPiCS-02 study demonstrated a statistically significant 3.2-month overall survival benefit for Trodelvy versus physician's choice chemotherapy (14.4 vs. 11.2 months; HR=0.79; p=0.02).
Trodelvy also showed a 34% reduction in disease progression risk with improved progression-free survival (5.5 vs. 4 months; HR=0.66; p=0.0003) in this heavily pre-treated patient population.
Gilead Sciences announced that the U.S. Food and Drug Administration has accepted for priority review the supplemental Biologics License Application for Trodelvy (sacituzumab govitecan-hziy) in adult patients with unresectable locally advanced or metastatic hormone receptor-positive, HER2-negative breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting. The FDA grants priority review for therapies that would represent significant improvements in safety or effectiveness compared to standard applications, with a Prescription Drug User Fee Act target action date set for February 2023.
Significant Survival Benefit Demonstrated
The supplemental application is based on positive results from the registrational Phase 3 TROPiCS-02 study, which met both its primary endpoint of progression-free survival and key secondary endpoint of overall survival. In the study of 543 patients, Trodelvy demonstrated a statistically significant and clinically meaningful 3.2-month improvement in overall survival compared to physician's choice of chemotherapy (median OS: 14.4 months vs. 11.2 months; hazard ratio=0.79; 95% CI: 0.65-0.96; p=0.02).
"It is outstanding to see a clinically meaningful survival benefit of over three months for patients with pre-treated HR+/HER2- metastatic breast cancer (search)," said Hope S. Rugo, MD, Professor of Medicine and Director, Breast Oncology and Clinical Trials Education at the University of California San Francisco Comprehensive Cancer Center. "Nearly all patients with HR+/HER2- metastatic breast cancer will develop resistance to endocrine-based therapies even in combination with targeted agents, so these data are welcome news for the breast cancer community."
Progression-Free Survival Benefits
The study also demonstrated significant improvements in progression-free survival, with Trodelvy showing a 34% reduction in risk of disease progression or death compared to comparator chemotherapy (median PFS: 5.5 versus 4 months; hazard ratio: 0.66; 95% CI: 0.53-0.83; p=0.0003). Other key secondary endpoints including objective response rate showed statistically significant improvement favoring Trodelvy versus physician's choice of treatment.
Quality of life measures also favored Trodelvy, with time to deterioration of Global Health Status/Quality of Life showing improvement (4.3 months vs. 3.0 months, p=0.006) and Fatigue scale benefits (2.2 months vs. 1.4 months, p=0.002) per EORTC-QLQ-C30 assessments.
Addressing Critical Unmet Need
Hormone receptor-positive/HER2-negative breast cancer represents the most common type of breast cancer, accounting for approximately 70% of all new cases or nearly 400,000 diagnoses worldwide each year. 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%. As patients become resistant to endocrine-based therapy, their primary treatment option is limited to single-agent chemotherapy, with poor prognosis in this setting.
"People with pre-treated HR+/HER2- metastatic breast cancer (search) who have progressed on endocrine-based therapies and chemotherapy have limited treatment options, and we look forward to working with the FDA to potentially make Trodelvy available to patients who need it most," said Bill Grossman, MD, PhD, Senior Vice President, Therapeutic Area Head, Gilead Oncology.
Study Design and Safety Profile
The TROPiCS-02 study is a global, multicenter, open-label, Phase 3 study that randomized 543 patients 1:1 to evaluate Trodelvy versus physicians' choice of chemotherapy (eribulin, capecitabine, gemcitabine, or vinorelbine) in patients with HR+/HER2- metastatic breast cancer (search) who were previously treated with endocrine therapy, CDK4/6 (search) inhibitors and two to four lines of chemotherapy for metastatic disease.
The safety profile for Trodelvy in TROPiCS-02 was consistent with prior studies, with no new safety concerns identified in this population. The drug carries a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea.
Expanding Treatment Landscape
With these results, Trodelvy has now demonstrated survival benefits in both pre-treated HR+/HER2- metastatic breast cancer (search) and second-line metastatic triple-negative breast cancer (search). The drug is currently approved in more than 35 countries for triple-negative breast cancer patients who have received two or more prior systemic therapies, and is also approved in the U.S. for locally advanced or metastatic urothelial cancer (search) under the accelerated approval pathway.
Trodelvy is a first-in-class Trop-2 (search) directed antibody-drug conjugate, with Trop-2 being a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and bladder cancers. The drug is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I (search) inhibitor payload.