The U.S. Food and Drug Administration (FDA) has accepted for priority review the supplemental Biologics License Application (sBLA) for sacituzumab govitecan-hziy (Trodelvy®; Gilead Sciences) for the treatment of adult patients with unresectable locally advanced or metastatic hormone receptor positive (HR+), human epidermal growth factor receptor 2 (HER2) negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.
Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer is the most common type of breast cancer and accounts 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 with HR+/HER2- metastatic breast cancer become resistant to endocrine-based therapy, their primary treatment option is limited to single-agent chemotherapy. In this setting, it is common to receive multiple lines of chemotherapy regimens over the course of treatment, and the prognosis remains poor.
Sacituzumab govitecan is a first-in-class Trop-2 directed antibody-drug conjugate or ADC. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and bladder cancers.
Sacituzumab govitecan is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the microenvironment.
The FDA grants priority review for therapies that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.
The Prescription Drug User Fee Act (PDUFA) target action date is currently set for February 2023.
“Sacituzumab govitecan has already changed the treatment landscape in second-line metastatic triple-negative breast cancer and pre-treated metastatic urothelial cancer, and today’s news marks our third supplemental application acceptance within the last two years,” noted Bill Grossman, MD, PhD, Senior Vice President, Therapeutic Area Head, Gilead Oncology.
“People with pre-treated HR+/HER2- metastatic breast cancer 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 sacituzumab govitecan available to patients who need it most.”
This sBLA is based on data from the registrational Phase 3 TROPiCS-02 study, which met its primary endpoint of progression-free survival (PFS) and key secondary endpoint of overall survival (OS) over comparator chemotherapy (treatment of physician’s choice (TPC) of chemotherapy).
The TROPiCS-02 study is a global, multicenter, open-label, Phase 3 study, randomized 1:1 to evaluate sacituzumab govitecan versus physicians’ choice of chemotherapy (eribulin, capecitabine, gemcitabine, or vinorelbine) in 543 patients with HR+/HER2- metastatic breast cancer who were previously treated with endocrine therapy, CDK4/6 inhibitors and two to four lines of chemotherapy for metastatic disease.
PFS data were presented at the 2022 ASCO Annual Meeting and published in the Journal of Clinical Oncology, and OS data were recently presented at annual congress of the European Society for Medical Oncology (ESMO).
In the study, sacituzumab govitecan demonstrated a 34% reduction in risk of disease progression or death (median PFS: 5.5 versus 4 months; hazard ratio [HR]: 0.66; 95% CI: 0.53-0.83; p=0.0003) and a 21% decrease in the risk of death compared to TPC (median OS: 14.4 months vs. 11.2 months; HR=0.789; 95% CI: 0.646-0.964; p=0.02).
The safety profile for sacituzumab govitecan in TROPiCS-02 was consistent with prior studies, with no new safety concerns identified in this population.
Sacituzumab govitecan has not been approved by any regulatory agency for the treatment of HR+/HER2- metastatic breast cancer. Its safety and efficacy have not been established for this indication.
Clinical Practice Guide
Sacituzumab govitecan-hziy is currently included in the National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®)i This includes a Category 1 recommendation for use in adult patients with second-line metastatic triple-negative breast cancer (defined as those who received at least two prior therapies, with at least one line for metastatic disease) and a Category 2A preferred recommendation based on PFS data from TROPiCS-02 for investigational use in HR+/HER2- advanced breast cancer after prior treatment including endocrine therapy, a CDK4/6 inhibitor and at least two lines of chemotherapy. It also has a Category 2A recommendation for use in locally advanced or metastatic bladder cancer after prior treatment with platinum and a checkpoint inhibitor.ii
Sacituzumab govitecan has a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea; please see below for additional Important Safety Information.
Study of Sacituzumab Govitecan-hziy Versus Treatment of Physician’s Choice in Participants With HR+/HER2- Metastatic Breast Cancer (TROPiCS-02) – NCT03901339
Highlights of Prescribing Information
Sacituzumab govitecan (Trodelvy®; Gilead Sciences) [Prescribing Information]
 Rugo HS, Bardia A, Marmé F, Cortes J, Schmid P, Loirat D, Olivier Trédan, Eva Ciruelos, et al. Sacituzumab Govitecan in Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer. Journal of Clinical Oncology 2022 40:29, 3365-3376
i Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer Version 4.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed October 2022. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
ii Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer Version 2.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed October 2022. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
Featured image:Women and the power to fight breast cancer Courtesy: © 2017 – 2022. Fotolia/Adobe. Used with permission.