Treatment with nivolumab, followed by ipilumab, produced significantly higher overall survival (OS) and objective response rates (ORR) than sunitinib alone among intermediate- and poor-risk patients with previously untreated advanced renal-cell carcinoma, according to results from a study published in the New England Journal of Medicine
The study, titled “Nivolumab plus Ipilmumab versus Sunitinib in Advanced Renal-Cell Cardinoma
,” was led by Robert J. Motzer, MD of the Memorial Sloan Kettering Cancer Society and Roswell Park Cancer Institute and sponsored by Bristol-Myers Squibb and Ono Pharmaceutical.
Sunitinib, a varcular endothelial growth factor receptor tyrosine kinase inhibitor, is the current standard of care for first-line treatment of advanced renal cell carcinoma.
Nivolumab, a programmed death 1 (PD-1) immune checkpoint inhibitor antibody, was approved for the treatment of the condition after treatment with antiangiogenic therapy, which was based on an overall survival benefit in March 2017. Ipilimumab is approved for treatment of metastatic melanoma and is an anti-cytotoxic T-lymphocyte-associated antigen 4 antibody. When administered subsequently, the two monotherapies have exhibited antitumor activity in patients with advanced renal cell carcinoma, whether they are previously treated or untreated.
The open-label, phase 3 trial randomized 1,096 patients from October 2014 through February 2016 in a 1:1 ratio to receive either nivolumab (3 mg per kilogram of body weight) plus ipilmumab (1 mg per kilogram) intravenously every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks, or sunitinib (50 mg) orally once daily for 4 weeks for a 6-week cycle.
In the trial, 550 patients received the nivolumab followed by ipilimumab, and 546 patients received sunitinib; 425 and 422, respectively, had intermediate or poor risk.
At median follow-up of 25.2 months in intermediate- and poor-risk patients, the 18-month survival rate was 75% with the combination therapy and 60% with sunitinib. Median OS was not reached with the former versus 26 months with sunitinib. The ORR was 42% versus 27%, and the complete response rate (CRR) was 9% versus 1%. Median PFS was 11.6 months and 8.4 months, respectively.
Treatment-related adverse events (AEs) occurred in 93.1% (n=509) of patients in the combination group and 97.4% (n=521) of patients in the sunitinib group; grade 2 or 4 AEs occurred in 46% (n=250) of patients and 63% (n=335) of patients, respectively. In the respective groups, treatment-related AEs leading to discontinuation occurred in 22% (n=121) and 12% (n=66) of the patients in the respective groups.
The safety profile of nivolumab plus ipilimumab was consistent with that in previous studies in multiple tumor types, including advanced renal cell carcinoma with a lower incidence of grade 3 and 4 treatment-related adverse events than observed with sunitinib. Additionally, as measured by the Functional Assessment of Cancer Therapy (FACT)-Kidney Symptom Index 19 (FKSI-19), patients reported a better health-related quality of life (QOL) with nivolumab plus ipilimumab than with sunitinib.
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- Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. NEJM. 2018;378:1277-1290. doi: 10.1056/NEJMoa1712126.