Abstract
First-line therapy with nivolumab plus ipilimumab has antitumor activity especially in PD-L1+ tumors.
Major finding: First-line therapy with nivolumab plus ipilimumab has antitumor activity especially in PD-L1+ tumors.
Concept: In an open-label phase I trial, adverse events were consistent with expected events from monotherapy.
Impact: Combined PD-1 and CTLA-4 blockade may be effective as first-line therapy in patients with NSCLC.
First-line platinum-based combination chemotherapy achieves responses in approximately 30% of patients with advanced non–small cell lung cancer (NSCLC) without targetable mutations, but moderate-to-severe toxicity is observed and responses are not typically durable. The anti–PD-1 antibody nivolumab has been shown to improve survival compared with chemotherapy in patients with previously treated advanced NSCLC, and combined treatment with the anti–CTLA-4 antibody ipilimumab has improved activity compared with nivolumab or ipilimumab alone in melanoma, prompting Hellmann and colleagues to evaluate nivolumab plus ipilimumab as first-line therapy in an open-label phase I trial in patients with advanced chemotherapy-nïve NSCLC. Overall, 77 patients were treated: 38 received nivolumab every 2 weeks plus ipilimumab every 12 weeks, and 39 received nivolumab every 2 weeks plus ipilimumab every 6 weeks. The primary outcome was frequency of adverse events and serious adverse events, and secondary outcomes included objective responses and progression-free survival. Partial responses were achieved in 18 of 38 (47%) patients in the every-12-weeks cohort and 15 of 40 (38%) of patients in the every-6-weeks cohort. Progression-free survival at 24 weeks was 68% in the every-12-weeks cohort and 47% in the every-6-weeks cohort. Further, among patients with 1% or more of tumor cells exhibiting PD-L1 expression, 12 of 21 (57%) in the every-6-weeks cohort and 13 of 23 (57%) in the every-12-weeks cohort achieved partial responses. Combination therapy was generally well tolerated, and adverse events were consistent with expectations based on adverse events observed after monotherapy. Treatment-related serious adverse events occurred in 32% of patients in the every-12-weeks cohort and 28% of patients in the every-6-weeks cohort. These findings indicate that first-line nivolumab plus ipilimumab has antitumor activity in patients with NSCLC and suggest that this combination may have comparable efficacy to standard chemotherapy with less toxicity, altogether supporting further clinical investigation, especially to treat patients with tumors expressing PD-L1.
Note: Research Watch is written by Cancer Discovery editorial staff. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/content/early/by/section.
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