The targeted therapy, nivolumab (Opdivo, Bristol Myers Squibb), improved median overall survival by 5.4 months among patients with previously treated renal cell carcinoma (RCC) compared to standard of care everolimus (Afinitor).
The targeted therapy, nivolumab (Opdivo, Bristol Myers Squibb), improved median overall survival by 5.4 months among patients with previously treated renal cell carcinoma (RCC) compared to standard of care everolimus (Afinitor). The results of the phase III CheckMate 025 randomized clinical trial were published in The New England Journal of Medicine.
The trial was stopped early, in July 2015, when patients in the nivolumab experimental arm were shown to have superior survival compared to those in the control arm.
Patients treated with the anti-PD-1 antibody had a 27% reduced risk of death compared to those patients treated with the mTOR inhibitor everolimus (P = .002). The study is the first, according to the manufacturer, Bristol Myers Squibb, to show a survival advantage of an immune checkpoint immunotherapy in RCC.
Patients treated with nivolumab also had a greater objective response rate, 25% compared to 5% of patients in the everolimus arm that responded to treatment (P < .001). Complete responses occurred in four patients in the nivolumab arm and in two patients in the everolimus arm. The median progression-free survival (PFS) was 4.6 months in the nivolumab arm compared to 4.4 months in the everolimus arm (P = .11).
While patients with metastatic RCC have several targeted options of therapy, including sorafenib (Nexavar) and sunitinib (Sutent), patients still develop resistance.
The open-label trial randomized 821 previously treated patients with metastatic RCC one to one to either oral, daily everolimus-the recommended second- or third-line therapy-or 3 mg/kg of nivolumab infused every 2 weeks. The primary trial endpoint was overall survival. Patients had a median age of 62 and were predominantly Caucasian men.
The most common treatment-related adverse events among patients who were treated with nivolumab were fatigue (33% of patients), nausea (14%), and pruritus (14%). Patients in the everolimus arm experienced fatigue (34%), stomatitis (29%), and anemia (24%). High-grade treatment-related adverse events occurred in 76 of the 406 patients (19%) in the nivolumab arm and in 145 of the 397 patients (37%) treated with everolimus. The most common grade 3 or grade 4 event was fatigue (2%) with
nivolumab and anemia (8%) with everolimus. There were no deaths from drug related toxicity reported in the nivolumab arm and two in the everolimus arm (one from septic shock and one from acute bowel ischemia).
“The benefit from these agents, as compared with everolimus, is unequivocal,” wrote David I. Quinn, MB, BS, PhD, of the University of Southern California Norris Comprehensive Cancer Center in Los Angeles and Primo N. Lara Jr, MD, of the University of California Davis Comprehensive Cancer Center in Sacramento, Calif., in an accompanying editorial. “Given the overall survival advantage it confers and its relatively good side effect profile, nivolumab is the choice for patients who have disease progression while they are receiving VEGF-targeted therapy,” the authors added.