A meta-analysis of two pivotal phase 3 trials has confirmed that sacituzumab govitecan-hziy (SG, Trodelvy; Gilead Sciences) delivers significantly improved outcomes for patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) compared to treatment of physician's choice (TPC).
The retrospective analysis, which pooled individual participant data from the TROPiCS-02 (NCT03901339) and EVER-132-002 (NCT04639986) trials, provides compelling evidence of clinically significant improvements in both progression-free survival (PFS) and overall survival (OS) for patients receiving SG therapy, including those previously treated with CDK4/6 inhibitors and fast-progressors.
Disease Burden and Treatment Landscape
Breast cancer remains a significant global health challenge, with approximately 2.3 million new diagnoses worldwide in 2022. The HR+/HER2- subtype accounts for roughly 70% of all breast cancer cases, with nearly 30% of patients eventually developing metastatic disease despite initial early-stage diagnosis.
While advances in treatment have improved symptom management and slowed disease progression, resistance to first-line therapies continues to present a major obstacle for effective treatment.
Mechanism and Approval History
Sacituzumab govitecan is a Trop-2-targeting antibody-drug conjugate designed to deliver cytotoxic agents precisely to breast cancer cells while minimizing damage to surrounding healthy tissue. The FDA first approved SG in 2021 as a monotherapy for patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who had received two or more prior systemic therapies.
This initial approval was based on positive data from the phase 3 ASCENT trial (NCT02574455), which demonstrated superior PFS with SG compared to single-agent chemotherapy.
Meta-Analysis Methodology and Findings
The meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Individual Participant Data guidelines. Researchers evaluated individual participant data from both trials for integrity, consistency, imbalances, and missing values before pooling the data to estimate treatment effects.
The analysis compared outcomes across multiple efficacy endpoints, including OS, PFS, duration of response, objective response rate, and clinical benefit rate. Researchers examined these metrics in the overall population as well as in specific subgroups, particularly patients pretreated with CDK4/6 inhibitors and fast-progressors (defined as those with a prior CDK4/6 inhibitor treatment duration of 12 months or less).
"This research strengthens the case for incorporating SG into clinical practice guidelines, offering a promising therapeutic option for managing this disease," noted the study authors in their publication in Therapeutic Advances in Medical Oncology on March 14, 2025.
Real-World Efficacy Confirmation
Complementing these findings, a separate retrospective analysis presented at the 42nd Annual Miami Breast Cancer Conference demonstrated that sacituzumab govitecan shows similar efficacy and safety in real-world patients with metastatic triple-negative breast cancer (mTNBC) compared to clinical trial results.
The real-world study, which analyzed data from 409 patients who received SG in the second-line or later setting, reported a median overall survival of 11.3 months (95% CI, 10.0-12.8) at a median follow-up of 10.0 months. The median real-world progression-free survival was 5.0 months (95% CI, 4.4-5.5).
"Safety and efficacy are consistent with previous findings, even in this racially diverse real-world population with more patients at higher ECOG performance status compared to pivotal clinical trials," explained lead study author Vikram C. Gorantla, MD, of the University of Pittsburgh Medical Center Hillman Cancer Center.
Safety Profile
The real-world analysis reported neutropenia in 68.7% of patients, with a median time to onset of 8 days after SG initiation. Approximately 60.4% of patients received granulocyte colony-stimulating factor during treatment, either as primary prophylaxis (21.5%), secondary prophylaxis (27.4%), or as treatment for neutropenia (11.5%).
The most commonly reported adverse effects included fatigue (47.4%), diarrhea (38.1%), neutropenia (34.7%), and nausea (32.0%). These findings align with the safety profile observed in clinical trials, suggesting that SG maintains a manageable toxicity profile in diverse real-world populations.
Clinical Implications
The combined evidence from both the meta-analysis and real-world data provides strong support for sacituzumab govitecan's role in treating both HR+/HER2- metastatic breast cancer and metastatic triple-negative breast cancer.
For patients with HR+/HER2- mBC who have progressed on standard therapies, particularly those previously treated with CDK4/6 inhibitors, these findings suggest that SG offers a significant survival advantage over physician's choice treatment options.
The consistent efficacy demonstrated across both controlled clinical trials and real-world settings reinforces sacituzumab govitecan's potential to address the substantial unmet need in these challenging breast cancer subtypes, potentially reshaping treatment algorithms and improving outcomes for patients with limited therapeutic options.
