Pembrolizumab (PD-1) + radiotherapy MDT trends toward longer PFS in oligometastatic ccRCC

Radiotherapy-based metastasis-directed therapy (MDT) with or without pembrolizumab maintenance was compared in a pooled, exploratory analysis of two prospective single-arm Phase 2 trials (MDT+ICI: NCT02855203; MDT alone: NCT03575611) in oligometastatic clear cell RCC (n=150; 30 vs 120). After median follow-up of 34 months, MDT+pembrolizumab showed a numerically longer RECIST PFS vs MDT alone that narrowly missed statistical significance (HR 0.57, 95% CI 0.32–1.02; p=0.058) despite a higher baseline metastatic burden (median 3 vs 1 metastases), with interaction testing suggesting larger benefit in patients previously treated with systemic therapy. Immune correlatives favored combination therapy (more frequent induction of activated ICOS+ CD8+ T cells and decreases in less functional CD8+ subsets); toxicity details were not provided here—so any “maintenance ICI” tradeoff vs MDT alone can’t be weighed, but pembrolizumab’s immune-related AEs remain a real consideration in otherwise asymptomatic oligometastatic patients (and KEYNOTE-564’s M1 NED subgroup DFS signal [HR ~0.28] is a relevant benchmark for “post-local therapy” PD-1 benefit).