Across both favorable and intermediate/poor risk cohorts, a consistent pattern emerged: TKI–ICI combinations were more likely to yield durable (PFS ≥ 24 months) and extreme durable (PFS ≥ 36 months) responses than dual ICI therapy.
However, the lack of significant differences in 48-month overall survival across regimens suggests an important nuance. Despite higher rates of prolonged PFS with certain combinations, long-term survival curves ultimately converge, highlighting the potential influence of subsequent therapies, patient selection, and underlying disease biology.
For clinicians, these results underscore the importance of balancing durability with toxicity, comorbidities, patient goals, and quality-of-life considerations when choosing frontline therapy. For researchers, the findings reinforce the urgent need for predictive biomarkers that can distinguish patients who truly benefit from early intensive TKI–ICI strategies versus those who may derive comparable long-term survival with dual ICI or alternative sequencing. As frontline options continue to expand, identifying the patients most likely to experience meaningful, durable benefit remains central to advancing personalized care in metastatic RCC.
Written by:
- Pedro C. Barata, MD, MSc, FACP, Miggo Family Chair in Cancer Research, Co-Leader Genitourinary (GU) Disease Team, Director of GU Medical Oncology Research Program, University Hospitals Seidman Cancer Center, Associate Professor of Medicine, Case Western Reserve University, Case Comprehensive Cancer Center, Cleveland, OH
- Albert Jang, MD, Advanced Genitourinary Medical Oncology Fellow, Mayo Clinic, Rochester, Minnesota
- Jakob Nypaver, MD, MSc, Internal Medicine Resident, University Hospitals Cleveland Medical Center, Cleveland, OH