Bernard Escudier1, Padmanee Sharma2, David F McDermott3, Saby George4, Hans J Hammers5, Sandhya Srinivas6, Scott S Tykodi7, Jeffrey A Sosman8, Giuseppe Procopio9, Elizabeth R Plimack10, Daniel Castellano11, Howard Gurney12, Frede Donskov13, Katriina Peltola14, John Wagstaff15, Thomas C Gauler16, Takeshi Ueda17, Huanyu Zhao18, Ian M Waxman18, Robert J Motzer19. 1. Gustave Roussy, Villejuif, France. Electronic address: escudier@gustaveroussy.fr. 2. MD Anderson Cancer Center, University of Texas, Houston, TX, USA. 3. Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, MA, USA. 4. Roswell Park Cancer Institute, Buffalo, NY, USA. 5. Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA. 6. Stanford Cancer Institute, Stanford, CA, USA. 7. University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 8. Vanderbilt University Medical Center, Nashville, TN, USA. 9. Fondazione Istituto Nazionale Tumori, Milan, Italy. 10. Fox Chase Cancer Center, Philadelphia, PA, USA. 11. Hospital Universitario 12 De Octubre, Madrid, Spain. 12. Westmead Hospital, Westmead, NSW, Australia. 13. Aarhus University Hospital, Aarhus, Denmark. 14. Comprehensive Cancer Center, Helsinki University Central Hospital Cancer Center, Helsinki, Finland. 15. South West Wales Cancer Institute and Swansea University College of Medicine, Swansea, UK. 16. University Hospital Essen of University of Duisburg-Essen, Essen, Germany. 17. Chiba Cancer Center, Chiba, Japan. 18. Bristol-Myers Squibb, Princeton, NJ, USA. 19. Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Abstract
BACKGROUND: The randomized, phase 3 CheckMate 025 study of nivolumab (n=410) versus everolimus (n=411) in previously treated adults (75% male; 88% white) with advanced renal cell carcinoma (aRCC) demonstrated significantly improved overall survival (OS) and objective response rate (ORR). OBJECTIVE: To investigate which baseline factors were associated with OS and ORR benefit with nivolumab versus everolimus. DESIGN, SETTING, AND PARTICIPANTS: Subgroup OS analyses were performed using Kaplan-Meier methodology. Hazard ratios were estimated using the Cox proportional hazards model. INTERVENTION: Nivolumab 3mg/kg every 2 wk or everolimus 10mg once daily. RESULTS AND LIMITATIONS: The minimum follow-up was 14 mo. Baseline subgroup distributions were balanced between nivolumab and everolimus arms. Nivolumab demonstrated an OS improvement versus everolimus across subgroups, including Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium risk groups; age <65 and ≥65 yr; one and two or more sites of metastases; bone, liver, and lung metastases; number of prior therapies; duration of prior therapy; and prior sunitinib, pazopanib, or interleukin-2 therapy. The benefit with nivolumab versus everolimus was noteworthy for patients with poor MSKCC risk (hazard ratio 0.48, 95% confidence interval 0.32-0.70). The mortality rate at 12 mo for all subgroups was lower with nivolumab compared with everolimus. ORR also favored nivolumab. The incidence of grade 3 or 4 treatment-related adverse events across subgroups was lower with nivolumab. Limitations include the post hoc analysis and differing sample sizes between groups. CONCLUSION: The trend for OS and ORR benefit with nivolumab for multiple subgroups, without notable safety concerns, may help to guide treatment decisions, and further supports nivolumab as the standard of care in previously treated patients with aRCC. PATIENT SUMMARY: We investigated the impact of demographic and pretreatment features on survival benefit and tumor response with nivolumab versus everolimus in advanced renal cell carcinoma (aRCC). Survival benefit and response were observed for multiple subgroups, supporting the use of nivolumab as a new standard of care across a broad range of patients with previously treated aRCC. The trial is registered on ClinicalTrials.gov as NCT01668784.
RCT Entities:
BACKGROUND: The randomized, phase 3 CheckMate 025 study of nivolumab (n=410) versus everolimus (n=411) in previously treated adults (75% male; 88% white) with advanced renal cell carcinoma (aRCC) demonstrated significantly improved overall survival (OS) and objective response rate (ORR). OBJECTIVE: To investigate which baseline factors were associated with OS and ORR benefit with nivolumab versus everolimus. DESIGN, SETTING, AND PARTICIPANTS: Subgroup OS analyses were performed using Kaplan-Meier methodology. Hazard ratios were estimated using the Cox proportional hazards model. INTERVENTION: Nivolumab 3mg/kg every 2 wk or everolimus 10mg once daily. RESULTS AND LIMITATIONS: The minimum follow-up was 14 mo. Baseline subgroup distributions were balanced between nivolumab and everolimus arms. Nivolumab demonstrated an OS improvement versus everolimus across subgroups, including Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium risk groups; age <65 and ≥65 yr; one and two or more sites of metastases; bone, liver, and lung metastases; number of prior therapies; duration of prior therapy; and prior sunitinib, pazopanib, or interleukin-2 therapy. The benefit with nivolumab versus everolimus was noteworthy for patients with poor MSKCC risk (hazard ratio 0.48, 95% confidence interval 0.32-0.70). The mortality rate at 12 mo for all subgroups was lower with nivolumab compared with everolimus. ORR also favored nivolumab. The incidence of grade 3 or 4 treatment-related adverse events across subgroups was lower with nivolumab. Limitations include the post hoc analysis and differing sample sizes between groups. CONCLUSION: The trend for OS and ORR benefit with nivolumab for multiple subgroups, without notable safety concerns, may help to guide treatment decisions, and further supports nivolumab as the standard of care in previously treated patients with aRCC. PATIENT SUMMARY: We investigated the impact of demographic and pretreatment features on survival benefit and tumor response with nivolumab versus everolimus in advanced renal cell carcinoma (aRCC). Survival benefit and response were observed for multiple subgroups, supporting the use of nivolumab as a new standard of care across a broad range of patients with previously treated aRCC. The trial is registered on ClinicalTrials.gov as NCT01668784.
Authors: Bernard Escudier; Thomas Powles; Robert J Motzer; Thomas Olencki; Osvaldo Arén Frontera; Stephane Oudard; Frederic Rolland; Piotr Tomczak; Daniel Castellano; Leonard J Appleman; Harry Drabkin; Daniel Vaena; Steven Milwee; Jillian Youkstetter; Julie C Lougheed; Sergio Bracarda; Toni K Choueiri Journal: J Clin Oncol Date: 2018-01-08 Impact factor: 44.544
Authors: Toni K Choueiri; Sabina Signoretti; Abdallah Flaifel; Wanling Xie; David A Braun; Miriam Ficial; Ziad Bakouny; Amin H Nassar; Rebecca B Jennings; Bernard Escudier; Daniel J George; Robert J Motzer; Michael J Morris; Thomas Powles; Evelyn Wang; Ying Huang; Gordon J Freeman Journal: Clin Cancer Res Date: 2019-08-01 Impact factor: 12.531
Authors: Osama Mohamad; Alberto Diaz de Leon; Samuel Schroeder; Andrew Leiker; Alana Christie; Elizabeth Zhang-Velten; Lakshya Trivedi; Saad Khan; Neil B Desai; Aaron Laine; Kevin Albuquerque; Puneeth Iyengar; Yull Arriaga; Kevin Courtney; David E Gerber; Hans Hammers; Hak Choy; Robert Timmerman; James Brugarolas; Raquibul Hannan Journal: Oncoimmunology Date: 2018-03-15 Impact factor: 8.110