Outcomes for patients in the pembrolizumab+axitinib arm with advanced renal cell carcinoma (RCC) who completed two years of treatment in the phase III KEYNOTE-426 study.

327 Background: In the randomized, open-label, phase III KEYNOTE-426 study (NCT02853331), pembrolizumab + axitinib significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) versus sunitinib as first-line therapy for advanced RCC. Per protocol, patients could discontinue pembrolizumab or axitinib and continue the other agent. Pembrolizumab was stopped for all patients at 2 years. Axitinib could be continued until progression or toxicity. This exploratory subgroup analysis of KEYNOTE-426 describes outcomes of patients who completed 2 years of pembrolizumab. Methods: Patients included in KEYNOTE-426 were treatment naive, with clear cell RCC, KPS ≥70%, and measurable disease (RECIST v1.1). Patients were randomly assigned 1:1 to receive pembrolizumab 200 mg intravenously every 3 weeks for up to 35 doses + axitinib 5 mg orally twice daily or sunitinib 50 mg once daily (4 weeks on/2 weeks off) until progression, toxicity, or withdrawal. Primary end points of the original analysis were OS and PFS. Key secondary end points were ORR and safety. Results: Of 432 patients treated with pembrolizumab + axitinib, 129 (29.9%) completed 2 years of study therapy. Median (range) age of these patients was 61 (36-82) years, and 72.1% were male; 42 (32.6%) and 87 (67.4%) patients had International mRCC Database Consortium favorable and intermediate/poor risk, respectively, consistent with the intention-to-treat population (31.9% vs 68.1%). Median (range) follow-up (time from randomization to data cutoff) was 31.1 (24.0-37.7) months. For patients who completed 2 years of study therapy, the OS rates at 36 months was 93.8% (95% CI, 85.5%-97.4%). The PFS rates at 24 and 36 months were 72.7% (95% CI, 64.0%-79.7%) and 57.7% (95% CI, 46.3%-67.5%), respectively. The ORR was 85.3%, and the CR rate was 14.0%. 59.7% of patients experienced grade 3-5 treatment-related adverse events and 8.5% experienced grade 3-5 immune-mediated adverse events. Conclusions: In this exploratory analysis, a significant proportion of patients in the pembrolizumab + axitinib arm completed 2 years of pembrolizumab with ongoing clinical benefit. Clinical trial information: NCT02853331 .