Meta-Analysis of Phase 3 Trials Support Use of Sacituzumab Govitecan Over Physician’s Choice Treatment

A meta-analysis of study results from the phase 3 TROPiCS-02 (NCT03901339) and EVER-132-002 (NCT04639986) trials confirms that sacituzumab govitecan-hziy (SG, Trodelvy; Gilead Sciences) significantly improves outcomes in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC), including those pretreated with CDK4/6 inhibitors and fast-progressors compared with treatment of physician's choice (TPC). The data supports existing evidence showing the clinically significant improvements in progression-free survival (PFS) and overall survival (OS) in patients receiving treatment with SG.^1,2

Illustration of targeted therapy molecules | Image Credit: © Hikmet - stock.adobe.com

In 2022, approximately 2.3 million people worldwide were diagnosed with BC, with nearly 320,000 new cases expected in the United States by 2025. The most common subtype, HR+/HER2- BC, accounts for about 70% of all cases. Although many patients are initially diagnosed at an early stage, nearly 30% will eventually develop metastatic disease. Advances in treatment have helped manage symptoms and slow progression, but resistance to first-line therapies remains a major challenge.³

SG is a Trop-2-targeting antibody-drug conjugate that has significantly improved PFS and OS in patients with triple-negative breast cancer (TNBC). Its targeted design enables precise delivery to breast cancer cells while minimizing damage to surrounding healthy tissue. It was approved by the FDA for multiple indications; in 2021, it was first approved as a monotherapy for patients with unresectable locally advanced or metastatic TNBC who have received 2 or more prior systemic therapies. This decision was based on positive data from the phase 3 ASCENT trial (NCT02574455), which showed SG therapy yielded greater PFS benefits when compared with single-agent chemotherapy.^4,5

In the retrospective meta-analysis of the TROPiCS-02 and EVER-132-002 trials, investigators compared the efficacy outcomes of SG to TPC in each trial. Their findings extend previous research and support the integration of SG into global clinical practice guidelines for treatment of patients with HR+/HER2- mBC.⁶

The study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Individual Participant Data guidelines. Individual participant data from the trials were evaluated for integrity, consistency, imbalances, and missing values and then pooled to estimate treatment effects. These effects were compared across OS, PFS, duration of response, objective response rate, and clinical benefit rate in the overall population, as well as in subgroups of patients pretreated with CDK4/6 and fast-progressors (defined as those with a prior CDK4/6 inhibitor duration of less than or equal to 12 months).⁶

The meta-analysis of the trials provides compelling evidence supporting the use of SG as a significant treatment option for patients with HR+/HER2- mBC. The findings reinforce SG's ability to improve PFS and OS compared with TPC. This research strengthens the case for incorporating SG into clinical practice guidelines, offering a promising therapeutic option for managing this disease.

REFERENCES

1. Study of sacituzumab govitecan-hziy versus treatment of physician's choice in participants with HR+/​HER2- metastatic breast cancer (TROPiCS-02). Updated October 21, 2024. Accessed March 18, 2025. https://clinicaltrials.gov/study/NCT03901339

2. Asian study of sacituzumab govitecan (IMMU-132) in HR+/​HER2- metastatic breast cancer (mBC). Updated June 14, 2024. Accessed March 18, 2025. https://clinicaltrials.gov/study/NCT04639986

3. Vepdegestrant demonstrates progression-free survival in patients with ER+/HER2- metastatic breast cancer. Pharmacy Times. March 11, 2025. Accessed March 18, 2025. https://www.pharmacytimes.com/view/vepdegestrant-demonstrates-progression-free-survival-in-patients-with-er-her2--metastatic-breast-cancer

4. Navigating triple-negative breast cancer treatment with sacituzumab govitecan. Pharmacy Times. February 27, 2025. Accessed March 18, 2025. https://www.pharmacytimes.com/view/navigating-triple-negative-breast-cancer-treatment-with-sacituzumab-govitecan

5. Trial of sacituzumab govitecan in participants with refractory/​relapsed metastatic triple-negative breast cancer (TNBC) (ASCENT). Updated June 15, 2022. Accessed March 18, 2025. https://clinicaltrials.gov/study/NCT02574455

6. Gluz O, Xu B, Nanda R, et al. Efficacy of sacituzumab govitecan versus treatment of physician's choice in previously treated HR+ and HER2- mBC: a meta-analysis of TROPiCS-02 and EVER-132-002 trials. Ther Adv Med Oncol. March 14, 2025. doi:10.1177/17588359251320285