1. Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma (ccRCC): Analysis of progression after first subsequent therapy in KEYNOTE-426
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Powles, Thomas, Plimack, Elizabeth R., Stus, Viktor, Waddell, Tom, Gafanov, Rustem, Pouliot, Frederic, Nosov, Dmitry, Melichar, Bohuslav, Soulieres, Denis, Borchiellini, Delphine, Vynnychenko, Ihor, Mcdermott, Raymond S., Azevedo, Sergio Jobim, Tamada, Satoshi, Anna Kryzhanivska, Li, Chenxiang, Burgents, Joseph E., Molife, L. Rhoda, Rini, Brian I., and Bedke, Jens
- Subjects
Cancer Research ,Oncology - Abstract
4513 Background: The randomized, open-label, phase 3 KEYNOTE-426 study (NCT02853331) met its primary and key secondary end points of improved OS, PFS, and ORR with pembro + axi versus sunitinib as first-line treatment for patients with advanced ccRCC. Extended follow-up (42.8-mo median follow-up) continued to show the superior efficacy of pembro + axi versus sunitinib in this patient population. We describe the results of PFS2 for all randomly assigned patients and across IMDC risk categories. Methods: Treatment-naive patients with advanced ccRCC, Karnofsky Performance Status Scale score ≥70% and measurable disease per RECIST v1.1 were randomly assigned 1:1 to receive pembro 200 mg IV every 3 weeks for up to 35 doses (̃2 y) + axi 5 mg orally twice daily or sunitinib 50 mg orally once daily on a 4-wk on/2-wk off schedule. The end point of this exploratory analysis was PFS2, defined as time from randomization to progression after first subsequent therapy or any-cause death. The Kaplan-Meier method was used to estimate PFS2 and hazard ratios were estimated using a Cox regression model. Results: Of 861 patients, 432 were assigned to receive pembro + axi; 429, to sunitinib. Median time from randomization to the database cutoff date (January 11, 2021) was 42.8 mo (range, 35.6-50.6). Overall, 47.2% of patients (204/432) in the pembro + axi arm and 65.5% of patients (281/429) in the sunitinib arm received ≥1 line of subsequent anticancer therapy. For patients who received subsequent therapy, anti–PD-1/PD-L1 agents were the first subsequent treatment for 11.3% of patients (23/204) in the pembro + axi arm and 54.8% of patients (154/281) in the sunitinib arm. In the pembro + axi arm, 82.8% of patients (169/204) received a VEGF/VEGFR inhibitor as first subsequent therapy, as did 43.4% (122/281) in the sunitinib arm. PFS2 results are displayed in the Table. Conclusions: In this exploratory analysis, PFS2 was longer for patients randomized to pembro + axi compared to sunitinib. Results were consistent across IMDC risk groups. These data support use of pembro + axi for the first-line treatment of patients with advanced ccRCC. Clinical trial information: NCT02853331. [Table: see text]