Progression-Free and Overall Survival Outcomes

PFS and OS Outcomes

The KEYNOTE-B61 study demonstrated impressive PFS outcomes with a median PFS of 17.9 months, representing approximately a year and a half of disease control for patients with advanced non–clear cell RCC. When analyzed by histologic subtype, papillary RCC showed a median PFS of 17.7 months, while patients with chromophobe RCC appeared to have different survival kinetics, likely reflecting the more indolent natural history of this particular subtype. The consistent PFS benefit across the heterogeneous non–clear cell population reinforces the broad applicability of this treatment combination across different histologic variants.

The overall survival data, which was newly presented in July 2025, revealed a median OS of 41.5 months for all patients treated with pembrolizumab plus lenvatinib. This represents a remarkable achievement in a historically challenging patient population. When broken down by histologic subtype, papillary RCC showed a median OS of 37.5 months, while the median OS for chromophobe RCC was not yet reached, again reflecting the more indolent course that characterizes this particular histology and suggesting potentially even more favorable long-term outcomes for these patients.

These survival outcomes represent a transformative improvement over historical benchmarks established during the TKI era. Cross-trial comparisons reveal that pembrolizumab plus lenvatinib essentially doubled all key efficacy measures compared with previous standard treatments. Historical TKI monotherapy studies, including trials with sunitinib and everolimus, typically achieved a median PFS of only 8 to 9 months at best. Similarly, median OS with TKI-based treatments was approximately 21 months, primarily demonstrated in papillary RCC studies. The KEYNOTE-B61 results show a 100% improvement across all major efficacy end points, establishing a new paradigm for treatment expectations in advanced non–clear cell RCC.