Multiple targeted therapies including angiogenesis and mTOR inhibitors are recommended for patients with advanced renal cell carcinoma. However for patients with advanced disease who have received multiple lines of therapy, achieving a survival benefit can be very challenging.
A new study by Motzer et al. published in the New England Journal of Medicine, reported the results of the randomized phase III Checkmate025 study comparing the mTOR inhibitor everolimus to the PD-1 inhibitor nivolumab in patients with clear cell renal cell carcinoma who have previously received up to two antiangiogenic regimens.
The study enrolled 821 patients randomized to receive either 3m/kg of body weight of nivolumab every 2 weeks or 10 mg of oral everolimus daily. The study clearly demonstrated an overall survival advantage for nivolumab versus everolimus (21.8 versus 19.6 months. The hazard ratio for death with nivolumab versus everolimus was 0.73 (98.5% CI, 0.57 to 0.93; P = 0.002) showing superiority for nivolumab. In addition to be more, efficacious, nivolumab also had a favorable toxicity profile in comparison with everolimus (19 % versus 37 % grade 3 or 4 treatment-related adverse events respectively). The study was stopped early after interim analysis after the study met its overall survival primary endpoint.
The survival benefit observed with nivolumab was consistent across patients with different MSKCC prognostic scores and different numbers of previous antiangiogenic therapies. Interestingly, the benefit from nivolumab was achieved irrespective of PD-1 expression suggesting that PD-1 may not be a biomarker for response to nivolumab in renal cell carcinoma.
The findings of this landmark study firmly places nivolumab on the therapeutic map for patients progressing on VEGF-targeted therapy.
References:
Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. DOI: 10.1056/NEJMoa1510665 Read Article Abstract
Commenatry written by: Bishoy Faltas Dr. Bishoy Faltas is a medical oncologist in New York, New York and is affiliated with New York-Presbyterian University Hospital of Columbia and Cornell.