Nivolumab superior to everolimus for pretreated advanced renal cell carcinoma

Issue: December 25, 2017

MIAMI — Nivolumab induced more durable responses than everolimus among patients with advanced renal cell carcinoma, according to 3-year follow-up data from the phase 3 CheckMate 025 study presented at International Kidney Cancer Symposium.

The study included 821 adults with advanced clear cell renal cell carcinoma whose disease progressed after one or two prior antiangiogenic therapies.

Padmanee Sharma, MD, PhD, of the department of genitourinary medical oncology at The University of Texas MD Anderson Cancer Center, and colleagues randomly assigned patients to the PD-1 checkpoint inhibitor nivolumab (Opdivo, Bristol-Myers Squibb) 3 mg/kg via IV every 2 weeks or the mTOR inhibitor everolimus (Afinitor, Novartis) 10 mg daily.

Treatment continued until progression or unacceptable toxicity.

OS served as the primary endpoint. Key secondary endpoints included objective response rate, PFS and adverse events.

At 14 months follow-up, patients assigned nivolumab achieved longer median OS (25 months vs. 19.6 months) and a higher ORR (25% vs. 5%).

At the International Kidney Cancer Symposium, Sharma and colleagues presented an updated analysis with 3-year efficacy and safety data. The analysis included data from 803 treated patients, of whom 406 received nivolumab and 397 received everolimus.

Minimum follow-up was 38 months. At data cutoff, 27 (7%) patients assigned nivolumab and three (< 1%) patients assigned everolimus remained on treatment.

Median treatment duration was 5.5 months (range, 5.1-6.9) with nivolumab and 3.7 months (range, 3.3-4.1) with everolimus. The majority of patients who discontinued treatment did so because of progression (77% with nivolumab vs. 74% with everolimus).

The updated data showed higher 2-year OS (52% vs. 42%) and 3-year OS (39% vs. 30%) in the nivolumab group. Median OS was 25.8 months (95% CI, 22.2-29.8) for nivolumab and 19.7 months (95% CI, 17.6-22.1) for everolimus (HR = 0.74; 95.45% CI, 0.63-0.88).

Researchers reported longer median PFS among everolimus-treated patients (4.5 months vs. 4.2 months; HR = 0.85; 95% CI, 0.73-0.99); however, results suggested a delayed PFS benefit with nivolumab.

More patients assigned nivolumab achieved complete response (1% vs. 0.5%) or partial response (25% vs. 5%). Nivolumab-treated patients also achieved longer median duration of response (12.3 months vs. 12 months).

At data cutoff, 18 of 106 (17%) responders in the nivolumab group and one of 22 (5%) responders in the everolimus group remained in ongoing response.

More patients assigned everolimus experienced any-grade treatment-related adverse events (89% vs. 80%), grade 3/grade 4 adverse events (37% vs. 21%), or adverse events that led to discontinuation (13% vs. 8%).

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Researchers reported the following resolution rates of nivolumab-related any-grade adverse events: pulmonary (85%), gastrointestinal (84%), hepatic (80%), skin (78%), renal (67%) and endocrine (38%).

Health-related quality of life from baseline to 140 weeks improved with nivolumab. Scores among everolimus-treated patients were consistently lower than scores for nivolumab-treated patients and declined from week 96 onward, researchers wrote.

More than two-thirds of patients in each treatment group received subsequent systemic therapy (68% for everolimus vs. 64% for nivolumab). – by Mark Leiser

For more information:

Sharma P, et al. Three-year efficacy and safety update from the phase III CheckMate 025 study of nivolumab versus everolimus in patients with advanced renal cell carcinoma. Presented at: International Kidney Cancer Symposium; Nov. 3-4, 2017; Miami.

Disclosure: Bristol-Myers Squibb funded this study. The authors report no relevant financial disclosures.