Axitinib plus pembrolizumab in patients with advanced renal-cell carcinoma: Long-term efficacy and safety from a phase Ib trial

Abstract

Background: Axitinib plus pembrolizumab showed superior overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) versus sunitinib in a randomised phase III trial in patients with advanced renal-cell carcinoma (RCC). We report long-term efficacy and safety of the axitinib/pembrolizumab from the phase I trial (NCT02133742), after 46-55 months from study initiation (data cut-off date, 23rd July 2019).

Methods: Fifty-two treatment-naïve patients with advanced RCC were treated with oral axitinib 5 mg twice daily and intravenous pembrolizumab 2 mg/kg every 3 weeks. PFS, duration of response (DoR) and OS were summarised using the Kaplan-Meier method.

Results: At a median follow-up of 42.7 months (95% confidence interval [CI]: 41.1-44.1), median OS was not reached; 38 (73.1%) patients were alive. The probability of being alive at 4 years was 66.8% (95% CI: 49.1-79.5). Median PFS in the overall population was 23.5 months (95% CI: 15.4-30.4). ORR was 73.1%; five patients had complete response. Median DoR was 22.1 months (95% CI: 15.1-34.5). Grade III/IV adverse events (AEs) were reported in 38 (73.1%) patients and 20 (38.5%) discontinued treatment because of AEs: 17 (32.7%) discontinued axitinib, 13 (25.0%) discontinued pembrolizumab, and 10 (19.2%) discontinued both drugs. Common AEs included diarrhoea (84.6%), fatigue (80.8%), hypertension (53.8%), cough (48.1%) and dysphonia (48.1%). There were no new AE terms reported and no treatment-related deaths.

Conclusions: In patients with advanced RCC with ~4 years of follow-up, combination axitinib/pembrolizumab continued to demonstrate clinical benefit, with no new safety signals.

Keywords: Axitinib; Long-term; Overall survival; Pembrolizumab; Progression-free survival; Renal-cell carcinoma; Safety.

Conflict of interest statement

Conflict of interest statement MB Atkins reports institutional research support from Bristol-Myers Squibb, Merck, Pfizer, and Genentech; consulting fees from Pfizer, Novartis, Genentech-Roche, Merck, Exelixis, Eisai, Boehringer Ingelheim, Aveo, Array, Idera, Aduro, Immunocore, Iovance, NewLink, Pharma, Surface, Alexion, Acceleron, COTA, Amgen, Up-to-Date, and AstraZeneca; roles in advisory boards for Bristol-Myers Squibb, Merck, Novartis, Arrowhead, Pfizer, Glactone, Werewolf, Fathom, Pneuma, Leads Pharma, Pyxis; and stock option in Werewolf and Pyxis. ER Plimack reports consulting fees from and/or served roles in advisory boards for Bristol-Myers Squibb, Exelixis, Genentech, Incyte, Janssen, Merck, AstraZeneca, and Pfizer; and grant or clinical trial support from Astellas, AstraZeneca, Bristol-Myers Squibb, Genentech, Merck, Peloton, and Pfizer. I Puzanov reports consulting fees from and/or served on advisory boards for Amgen, Roche, and AbbVie and clinical trial support through his institution from Merck, Amgen, Roche, Nektar, Idera, and Bristol-Myers Squibb. MN Fishman reports research funding from Bristol-Myers Squibb, Exelixis, Eisai, Genentech, Acceleron, Merck, Prometheus / Clinigen, Nektar, Alkermes, and Pfizer; and speakers bureau roles for Astellas, Bristol-Myers Squibb, Exelixis, EMD Serono, Pfizer; and paid roles in advisory boards for Alkermes, Clinigen, Eisai, Merck, Pfizer, Seattle Genetics. DF McDermott reports consulting fees from Bristol-Myers Squibb, Pfizer, Novartis, Genentech-Roche, Merck, Eisai, Array BioPharma, Prometheus, and Exelixis. DC Cho reports consulting fees from Pfizer, Genentech, Prometheus, Bristol-Myers Squibb, PureTech Health, Torque Pharmaceuticals, and Exelixis. U Vaishampayan reports research support from Astellas, Bristol-Myers Squibb, and Exelixis and consulting fees from Exelixis, Merck, Alkermes, Pfizer, Pfizer, Bayer, and Bristol-Myers Squibb. S George reports consulting fees from and advisory roles for Pfizer, Exelixis, Bristol-Myers Squibb, Sanofi/Genzyme, Genentech, Bayer, Corvus, EMD Serono, Seattle Genetics/Astellas, Eisai, and Merck and institutional grant support from Bristol-Myers Squibb, Novartis, Bayer, Pfizer, Merck, Seattle Genetics/Astellas, Eisai, Calithera Biosciences, Immunomedics, Corvus Pharmaceuticals, and Agensys. JC Tarazi, W Duggan, M Thakur, and KC Fernandez reports being employees of Pfizer and stock or stock options in Pfizer. R Perini reports an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. TK Choueiri reports research support (institutional and personal) from AstraZeneca, Alexion, Bayer, Bristol-Myers Squibb/E.R. Squibb & Sons LLC, Cerulean, Eisai, Foundation Medicine Inc, Exelixis, Ipsen, TRACON, Genentech, Roche, Roche Products Ltd, F. Hoffmann-La Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, Prometheus, Corvus, Calithera, Analysis Group, Sanofi/Aventis, Takeda, National Cancer Institute (NCI), National Institutes of Health (NIH), and Department of Defense (DOD); honoraria from AstraZeneca, Alexion, Sanofi/Aventis, Bayer, Bristol-Myers Squibb/E.R. Squibb & Sons LLC, Cerulean, Eisai, Foundation Medicine Inc, Exelixis, Genentech, Roche, Roche Products Ltd, F. Hoffmann-La Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus, Corvus, Ipsen, Up-to-Date, Analysis Group, National Comprehensive Cancer Network (NCCN), Michael J. Hennessy (MJH) Associates Inc, Research to Practice, Lpath, Kidney Cancer journal, Clinical Care Options, PlatformQ, Navinata Health, Harborside Press, American Society of Medical Oncology, New England Journal of Medicine, Lancet Oncology, Heron Therapeutics, Lilly, American Society of Clinical Oncology (ASCO), and European Society of Medical Oncology (ESMO); provided consultancy or advisory services to AstraZeneca, Alexion, Sanofi/Aventis, Bayer, Bristol-Myers Squibb/E.R. Squibb & Sons LLC, Cerulean, Eisai, Foundation Medicine Inc, Exelixis, Genentech, Heron Therapeutics, Lilly, Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus, Corvus, Ipsen, Up-to-Date, NCCB, Analysis Group, Pionyr, and Tempest; stock ownership in Pionyr and Tempest; contributions toward International Patent Application No. PCT/US2018/12,209, entitled “PBRM1 Biomarkers Predictive of Anti-Immune Checkpoint Response,” filed January 3, 2018, claiming priority to U.S. Provisional Patent Application No. 62/445,094, filed January 11, 2017, and International Patent Application No. PCT/US2018/058,430, entitled “Biomarkers of Clinical Response and Benefit to Immune Checkpoint Inhibitor Therapy,” filed October 31, 2018, claiming priority to U.S. Provisional Patent Application No. 62/581,175, filed November 3, 2017; and travel, accommodations, and expenses in relation to consulting, advisory roles, and/or honoraria.

Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.