Robert J. Motzer
Nivolumab plus ipilimumab improved OS and objective response rates compared with sunitinib among patients with intermediate- and poor-risk advanced renal-cell carcinoma, according to findings published in The New England Journal of Medicine.
“Approximately 75% of patients with advanced renal cell carcinoma have intermediate- or poor-risk disease and have worse outcomes than those with favorable-risk disease,” Robert J. Motzer, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, and colleagues wrote. “Combination therapy with nivolumab [Opdivo, Bristol-Myers Squibb] plus ipilimumab [Yervoy, Bristol-Myers Squibb] has shown promising efficacy in multiple tumor types, resulting in higher rates of response than either agent alone, and is approved for the treatment of advanced melanoma.”
The researchers conducted a phase 3 trial of 1,096 adults with intermediate- and poor-risk renal cell carcinoma. Motzer and colleagues randomly assigned patients to receive either nivolumab plus ipilimumab (n = 550) or sunitinib (Sutent, Pfizer; n = 546). OS, PFS and ORR served as coprimary endpoints.
Four hundred twenty-five patients had intermediate-risk, and 422 had poor risk.
Eighteen-month OS was 75% (95% CI, 70-78) among patients assigned nivolumab plus ipilimumab compared with 60% in the sunitinib group (95% CI, 55-65).
Median OS was not reached for the nivolumab plus ipilimumab group compared with 26 months for the sunitinib group (HR = 0.63; P < .0001).
Patients in the nivolumab plus ipilimumab group also demonstrated a significantly better ORR (42% vs. 27%; P < .001) and a better complete response rate (9% vs. 1%). This group also had a longer median PFS (11.6 months vs. 8.4 months; HR = 0.82; P = .03), but this was not significant with regard to the prespecified P-value threshold of .009.
Nearly all patients (93%) in the nivolumab plus ipilimumab group experienced treatment-related adverse events, as did 97% of patients in the sunitinib group. Grade 3 or grade 4 adverse events occurred in slightly less than half (46%) of the combination group compared with 63% of the sunitinib group.
Twenty-two percent of patients assigned nivolumab plus ipilimumab experienced treatment-related adverse events that led to discontinuation compared with 12% of patients assigned sunitinib.
Brendan D. Curti
In an accompanying editorial, Brendan D. Curti, MD, medical oncologist at Providence Cancer Institute in Portland, Oregon, described the findings as a step closer to a cure.
“During the past 25 years, treatment of renal cell carcinoma has evolved from infrequently effective cytokine-based immunotherapy to active but rarely curative tyrosine kinase inhibitor treatment, and now to more effective immunotherapy that, in some clinical settings, is superior to TKIs,” he wrote. “Even the current state of the art offers a modest probability of complete response or cure. The goal of future immunotherapy development should be not just transient response or tumor control, but rather cure in a higher proportion of patients. The combination of ipilimumab and nivolumab is a step in the right direction.” – by Andy Polhamus
Disclosures: Motzer reports grant support from Bristol-Myers Squibb during the conduct of the study; grant support and personal fees from Eisai, Exelixis, Novartis and Pfizer; and grant support from Genentech/Roche outside the submitted work. Please see the full study for all other authors’ relevant financial disclosures. Curti reports grants, personal fees, and nonfinancial support from Bristol-Myers Squibb and Prometheus, grants from MedImmune and Viralytics, and personal fees from Eisai outside the submitted work.