Immunotherapy with Nivolumab plus Ipilimumab for Patients with Metastatic Renal-Cell Carcinoma
Despite the advancements in targeted therapies for the management of patients with metastatic renal-cell carcinoma (mRCC), their prognosis remains poor, underscoring the need for novel treatment strategies. Combination therapy with the 2 immune checkpoint inhibitors, nivolumab, a fully human anti–programmed death-1 monoclonal antibody, and ipilimumab, a fully human cytotoxic T-lymphocyte antigen-4 monoclonal antibody, was shown to be effective in patients with advanced melanoma. Taken together with evidence of encouraging antitumor activity in mRCC, the combination of nivolumab and ipilimumab was evaluated in patients with mRCC.
Hammers and colleagues presented data from a trial of 54 patients with mRCC who were randomized to receive 1 of 2 treatments, either nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (N3 + I1; 21 patients), or nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (N1 + I3; 23 patients) every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg every 2 weeks until disease progression or until unacceptable toxicity(Hammers et al. ESMO 2014: Abstract 1050O). The primary objective was safety assessment; secondary objective was efficacy analysis by RECIST 1.1 criteria. Objective response rates were similar in the 2 treatment arms (N3 + I1, 43%; N1 + I3, 48%).
The median duration of response was 31.1 weeks in the N3 + I1 cohort, and was not yet reached in the N1 + I3 cohort. Median progression-free survival was similar between the 2 patient cohorts (36.6 vs 38.3 weeks, respectively). Responses occurred by first tumor assessment (6 weeks) in 44.4% and in 54.5%, respectively. The majority of the patients showed ongoing response to therapy at the time of this analysis (77.8% vs 81.8%, respectively), and their disease continued to respond even after treatment discontinuation that was not related to disease progression (33.3% vs 45.5%, respectively).
The adverse event profile was as previously described with this combination strategy in patients with melanoma; common toxicities were gastrointestinal disorders, hepatic toxicities, and endocrinopathies. Hammers and colleagues concluded that the grade 3 or 4 events, including diarrhea, and elevations in ALT or AST were largely manageable by using recommended treatment algorithms.
Overall, nivolumab plus ipilimumab combination therapy was associated with an acceptable toxicity and an encouraging antitumor activity in patients with mRCC. This strategy is the rationale for a planned phase 3 clinical trial for firstline treatment of patients with mRCC.