Nivolumab versus Everolimus in Advanced Renal Cell Carcinoma

By R. Motzer, B. Escudier, D. McDermott, S. George, H. Hammers, S. Srinivas, S. Tykodi, J. Sosman, G. Procopio, E. Plimack and 17 more. New England Journal of Medicine, 2015

5,232 citations recorded by the source corpus.

BACKGROUND Nivolumab, a programmed death-1 checkpoint inhibitor, demonstrated encouraging overall survival in uncontrolled studies in previously treated patients with advanced renal cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus in renal cell carcinoma after prior treatment. METHODS Eight hundred twenty-one patients with advanced clear-cell renal cell carcinoma previously treated with one or two antiangiogenic therapies were randomized (1:1) to receive nivolumab 3 mg/kg intravenously every 2 weeks or everolimus 10-mg tablet orally once daily. Primary end point was overall survival. Secondary end points included objective response rate and safety. RESULTS Median (95% confidence interval [CI]) overall survival was 25.0 months (21.8 to not estimable) with nivolumab and 19.6 months (17.6 to 23.1) with everolimus. The hazard ratio for risk of death with nivolumab versus everolimus was 0.73 (98.5% CI, 0.57 to 0.93; P=0.0018), meeting the predefined criterion for superiority (P≤0.0148). Objective response rate was greater with nivolumab (25%) than everolimus (5%; odds ratio 5.98; 95% CI, 3.68 to 9.72; P<0.001). Median (95% CI) progression-free survival was 4.6 months (3.7 to 5.4) with nivolumab and 4.4 months (3.7 to 5.5) with everolimus (hazard ratio, 0.88; 95% CI, 0.75 to 1.03; P=0.11). Grade 3 or 4 treatment-related adverse events occurred in 19% (nivolumab) and 37% (everolimus) of patients; most common was fatigue (3%) with nivolumab and anemia (8%) with everolimus. CONCLUSIONS Overall survival was longer and fewer grade 3 or 4 adverse events occurred for nivolumab versus everolimus in treatment-experienced patients with advanced renal cell carcinoma. ClinicalTrials.gov Identifier: NCT01668784

Subfields: Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/55372eb3737462f0d5f23e210198d6b2dfa2c1e8

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Citations in the corpus

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Management of toxicities of immune checkpoint inhibitors. (2016, background): “Activity of nivolumab has been demonstrated in pre-treated patients with metastatic renal cell carcinoma in both phase 2 and 3 trials [22,23].”
Treatment of renal cell carcinoma: Current status and future directions (2017, background): “Nivolumab (a PD-1 inhibitor) was the first checkpoint inhibitor to be investigated in a randomized, phase 3 trial (CheckMate-025) in a comparison with everolimus among 821 patients with advanced RCC who had received one or two prior lines of therapy.(55) The study showed a longer OS in favor of nivo”
Current Challenges in Cancer Treatment. (2016, background): “In patients with squamous-cell NSCLC and renal-cell carcinoma treated with nivolumab, RRs and OS improved irrespective of PD-L1 expression.(30,65) However, in non-squamous NSCLC, a strong predictive effect for PD-L1 expression was suggested.”