TNBC is an aggressive subtype that accounts for about 15% of breast cancers. Lacking estrogen, progesterone, and HER2 receptors, TNBC is harder to treat and has fewer therapeutic options. It carries a higher risk of early recurrence and metastasis, with an average time to metastatic recurrence of 2.6 years vs 5 years for other breast cancers. The five-year survival rate for mTNBC is just 12%, compared to 28% for other metastatic breast cancers.

While PD-1/PD-L1 inhibitors plus chemotherapy have improved options for PD-L1–positive advanced TNBC, outcomes remain poor. Sacituzumab govitecan has shown significant benefit in pretreated mTNBC and may help address this unmet need.

As of March 3, 2025, sacituzumab govitecan plus pembrolizumab (n = 221) improved median PFS to 11.2 months vs. 7.8 months with chemotherapy (cytotoxic agents) plus pembrolizumab (n = 222), reducing the risk of progression or death by 35% (HR 0.65; p < .001). Six- and 12-month PFS rates were higher in the sacituzumab arm (72% and 48%) vs chemotherapy (63% and 33%). OS data were immature (26% maturity) but favored sacituzumab despite 43% crossover from the chemotherapy arm. Median OS was not reached in either group; OS HR was 0.89. ORR was 60% with sacituzumab vs. 53% with chemotherapy. CR/PR rates were 13%/47% vs. 8%/45%. Median DOR was longer with sacituzumab (16.5 vs. 9.2 months); median time to response was 1.9 months in both arms. TEAEs occurred in >99% of patients; grade ≥3 in 71% (sacituzumab) vs. 70% (chemotherapy). Serious AEs: 38% vs. 31%; treatment-related: 28% vs. 19%. TEAEs led to discontinuation in 12% (sacituzumab) vs. 31% (chemotherapy); fatal TEAEs occurred in 3% of patients in both arms.

KOL insights: 

“The rate of SAEs was higher in the sacituzumab govitecan plus pembrolizumab group compared with the chemotherapy plus pembrolizumab group; however, the rate of TEAEs leading to dose reduction or treatment discontinuation was lower.” Expert Opinion.

Conclusion:

Sacituzumab govitecan plus pembrolizumab significantly improved PFS compared to chemotherapy plus pembrolizumab in patients with previously untreated, PD-L1–positive advanced TNBC, with a median PFS of 11.2 vs 7.8 months. This benefit was both statistically significant and clinically meaningful, accompanied by durable responses and a favorable safety profile. Notably, sacituzumab govitecan plus pembrolizumab was associated with fewer treatment discontinuations due to adverse events and no new safety signals. These findings support its potential role as a new standard of care in this high-risk population.