San Francisco, CA USA (UroToday.com) Dr. Motzer from Memorial-Sloan Kettering Cancer Center (MSKCC) presented subgroup analyses from the phase III CheckMate 025 clinical trial of nivolumab versus everolimus in advanced renal cell carcinoma (RCC). This study randomized 821 patients with previously treated advanced RCC with 1-2 vascular endothelial growth factor-directed therapies to either nivolumab (3 mg/kg IV every 2 weeks), a programmed death 1 receptor
(PD-1) inhibitor, or everolimus (10 mg orally once daily), an mTOR inhibitor approved by the Food and Drug Administration (FDA) for first-line treatment of non-clear cell RCC or second-line therapy following a tyrosine kinase inhibitor (TKI). CheckMate 025 was stopped early by an independent data monitoring committee after meeting its primary endpoint of improved overall survival (OS) with nivolumab (25.0 months; 95% CI [21.8, not evaluable]) versus everolimus (19.6 months; 95% CI [17.6, 23.1]) (hazard ratio (HR) 0.73; 98.5% CI [0.57, 0.93]; p = 0.002) and led to the FDA approval of nivolumab for previously treated advanced RCC in November 2015. In addition, the previously reported primary analysis demonstrated greater overall response rate (ORR) (25% versus 5%), and fewer grade 3-4 events (19% versus 37%), with nivolumab compared with everolimus in the overall study population.
Dr. Motzer provided an analysis of OS and ORR in key subgroups based on a variety of previously validated prognostic risk factors including number and sites of metastases, prior therapy, and time on first-line therapy. Nivolumab was favored over everolimus for both MSKCC and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) categories of prognostic risk scores, as well as number of sites of metastases and the presence of bone and liver metastases, both poor prognostic markers. He noted that the survival curves for intermediate and poor risk groups already showed separation, especially for poor risk disease, between nivolumab and everolimus treatment groups, and he predicted that the survival curves will separate more in the future for good risk groups. The most common prior therapy for study participants was sunitinib (63%) followed by pazopanib (32%), and both TKI treatment groups seemed to benefit equally from subsequent treatment with nivolumab. Subgroup analysis by number of lines of prior therapy and time on prior therapy favored nivolumab, including in those with the favorable variable. Interestingly, and in contrast with the experience with urothelial carcinoma, PD-1 status was not predictive of response to nivolumab. Future analyses will focus on outcomes based on subsequent anticancer therapy following study participation.
In summary, Dr. Motzer stated that nivolumab should be considered as a new standard of care for second line therapy following TKI treatment for advanced RCC based on its favorable ORR and OS compared with everolimus, as well as its superior safety profile. Consistent with the benefit observed in the overall study population, nivolumab demonstrated benefit in OS and ORR in clinically relevant subgroups of disease based on risk category, number and sites of metastases, and prior therapy.
Presented By:
Dr. Robert J. Motzer , MD
Memorial-Sloan Kettering Cancer Center (MSKCC)
Reported By:
Elizabeth A. Guancial, MD, at the 2016 Genitourinary Cancers Symposium - January 7 - 9, 2016 – San Francisco, CA
Assistant Professor - Department of Medicine, Hematology/Oncology
University of Rochester Medical Center School of Medicine and Dentistry