Background: In the phase 3 METEOR trial, cabozantinib improved progression-free survival (PFS), objective response rate (ORR), and overall survival (OS) versus everolimus in patients with advanced renal cell carcinoma (RCC), after prior antiangiogenic therapy. Methods: Outcomes were evaluated for subgroups defined by prior therapy with sunitinib or pazopanib as the only prior VEGFR inhibitor, or prior anti-PD-1/PD-L1 therapy. Results: For the prior sunitinib subgroup (N = 267), median PFS for cabozantinib versus everolimus was 9.1 versus 3.7 months (HR 0.43, 95% CI 0.32–0.59), ORR was 16% versus 3%, and median OS was 21.4 versus 16.5 months (HR 0.66, 95% CI 0.47–0.93). For the prior pazopanib subgroup (N = 171), median PFS for cabozantinib versus everolimus was 7.4 versus 5.1 months (HR 0.67, 95% CI 0.45–0.99), ORR was 19% versus 4%, and median OS was 22.0 versus 17.5 months (HR 0.66, 95% CI 0.42–1.04). For prior anti-PD-1/PD-L1 therapy (N = 32), median PFS was not reached for cabozantinib versus 4.1 months for everolimus (HR 0.22, 95% CI 0.07–0.65), ORR was 22% versus 0%, and median OS was not reached versus 16.3 months (HR 0.56, 95% CI 0.21–1.52). Conclusions: Cabozantinib was associated with improved clinical outcomes versus everolimus in patients with advanced RCC, irrespective of prior therapy, including checkpoint inhibitor therapy.
Bibliographical noteFunding Information:
Competing interests: T.P.: advisory/consulting role for AstraZeneca, Bristol-Myers Squibb (BMS), Genentech/Roche, Merck, Exelixis; research funding from AstraZeneca/ MedImmune, Roche/Genentech. R.J.M.: advisory/consulting role for Pfizer, Novartis, Eisai, Exelixis; research funding from BMS, Pfizer, Genentech/Roche, Eisai, Exelixis, Novartis. B.E.: advisory/consulting role for Novartis, BMS, Roche, Exelixis, Ipsen, Acceleron Pharma, Bayer; research funding from Novartis and BMS. S.P.: advisory/ consulting role for Novartis, Medivation Astellas Pharma, Pfizer, Aveo, Genentech, Exelixis, BMS, GlaxoSmithKline. C.K.: advisory/consulting role for Pfizer, BMS, Novartis, Astellas Pharma. H.G.: advisory/consulting role for Roche, MSD, Ipsen. M.G.G.: advisory/consulting role for Ipsen, Pfizer, BMS, Novartis. E.G.: advisory/consulting role for Ipsen, Pfizer, BMS, Eisai. C.S.: advisory/consulting role for BMS, Pfizer, Bayer, Ipsen; non-financial support from Pfizer and Astellas Pharma. D.W.M., A.A., M.D.: employees and stockholders of Exelixis. T.K.C.: advisory/consulting role for Pfizer, GlaxoSmithK-line, Novartis, Merck, Bayer, Eisai, Roche, Prometheus Labs, Foundation Medicine, BMS; research funding from Pfizer, GlaxoSmithKline, Novartis, BMS, Merck, Exelixis, Roche, AstraZeneca, Tracon, Peloton. D.G.: advisory/consulting role for Exelixis, BMS, Astellas Pharma, Dendreon, Innocrin, Pfizer, Sanofi, Bayer; research funding from Exelixis, BMS, Astellas Pharma, Dendreon, Innocrin, Janssen, Novartis, Pfizer, Bayer. All other authors declare no competing interests.
We thank the patients, their families, the investigators and site staff, and the study teams who participated in the METEOR trial. This study was funded by Exelixis, Inc. Patients treated at Memorial Sloan Kettering Cancer Center were supported in part by Memorial Sloan Kettering Cancer Center Support Grant/Core Grant (P30 CA008748). Editorial support was provided by Fishawack Communications (Con-shohocken, PA, USA) and funded by Exelixis.
© 2018, The Author(s).
All Science Journal Classification (ASJC) codes
- Cancer Research