Nivolumab Boosts Advanced ccRCC Overall Survival

Nivolumab extends overall survival in patients with advanced clear cell renal cell carcinoma compared with everolimus

medwireNews: CheckMate 025 trial results suggest that nivolumab offers superior overall survival to everolimus therapy in patients with advanced clear cell renal cell carcinoma (ccRCC) previously treated with one or two anti-angiogenic regimens.

The trial was halted early after the planned interim analysis showed the primary endpoint of overall survival was a superior median 25.0 months for the 410 patients randomly assigned to receive a 3 mg intravenous dose of the programmed death 1 (PD-1) inhibitor every 2 weeks compared with 19.6 months for the 411 patients given oral everolimus 10 mg/kg per day, giving a significant hazard ratio for death of 0.73.

Nivolumab-treated patients also had a significantly higher objective response rate than those given the mTOR inhibitor, at 25% versus 5% and an odds ratio (OR) of 5.98.

And although progression-free survival did not significantly differ between the nivolumab and everolimus groups, at 4.6 versus 4.4 months, the researchers note the “late separation” of this curve and suggest that this may indicate a delayed benefit for this endpoint.

The nivolumab-treated patients received the drug for a median of 5.5 months versus 3.7 months for the everolimus group, with dose delays in 51% and 66% of patients, respectively; nivolumab dose reduction was not permitted whereas everolimus reduction occurred in 26% of patients.

Treatment-related adverse events were reported in 79% of the nivolumab-treated patients – most commonly fatigue, nausea and pruritus – and 88% of the everolimus-treated patients, with the greatest number of reports pertaining to fatigue, stomatitis and anaemia.

Grade 3 and 4 treatment-related adverse events were reported in 19% and 37% of the nivolumab and everolimus groups, respectively, and adverse events led to discontinuation in a corresponding 8% and 13%.

The phase III trial was presented at the European Cancer Congress in Vienna, Austria, by Padmanee Sharma, from the MD Anderson Cancer Center in Houston, Texas, USA, and reported simultaneously in The New England Journal of Medicine.

Speaking at a press conference, Padmanee Sharma told medwireNews that there are no biomarkers to help select which advanced RCC patients should be considered for nivolumab use at this time.

Analysis showed that pre-treatment expression of programmed death ligand 1 (PD-L1) in tumour samples was comparable between the treatment arms and did not correlate with overall survival.

“The finding that overall survival was higher among patients treated with nivolumab, irrespective of PD-L1 expression, suggests that PD-L1 expression should not be used to determine which patients might respond to the therapy and whether or not to offer it to them”, Padmanee Sharma commented in a press release.

Noting that PD-L1 is a “dynamic” biomarker that changes with immune response, she added: “I would expect that tumour samples taken while patients were on-treatment, as opposed to pre-treatment, might indicate that PD-L1 expression, as well as other markers of immune response, has a correlation with response to treatment.”


Motzer RJ, Escudier B, McDermott DF et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015; Advance online publication 25 September. DOI: 10.1056/NEJMoa1510665

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