Phase III trial of ipilimumab combined with paclitaxel and carboplatin in advanced squamous non–small-cell lung cancer

Ramaswamy Govindan, Aleksandra Szczesna, Myung Ju Ahn, Claus Peter Schneider, Pablo Fernando Gonzalez Mella, Fabrice Barlesi, Baohui Han, Doina Elena Ganea, Joachim Von Pawel, Vladimir Vladimirov, Natalia Fadeeva, Ki Hyeong Lee, Takayasu Kurata, Li Zhang, Tomohide Tamura, Pieter E. Postmus, Jacek Jassem, Kenneth O’Byrne, Justin Kopit, Mingshun LiMarina Tschaika, Martin Reck

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230 Scopus citations

Abstract

Purpose Patients with squamous non–small-cell lung cancer (NSCLC) have poor prognosis and limited treatment options. This randomized, double-blind, phase III study investigated the efficacy and safety of first-line ipilimumab or placebo plus paclitaxel and carboplatin in advanced squamous NSCLC. Patients and Methods Patients with stage IV or recurrent chemotherapy-naïve squamous NSCLC were randomly assigned (1:1) to receive paclitaxel and carboplatin plus blinded ipilimumab 10 mg/kg or placebo every 3 weeks on a phased induction schedule comprising six chemotherapy cycles, with ipilimumab or placebo from cycles 3 to 6 and then, after induction treatment, ipilimumab or placebo maintenance every 12 weeks for patients with stable disease or better. The primary end point was overall survival (OS) in patients receiving at least one dose of blinded study therapy. Results Of 956 randomly assigned patients, 749 received at least one dose of blinded study therapy (chemotherapy plus ipilimumab, n = 388; chemotherapy plus placebo, n = 361). Median OS was 13.4 months for chemotherapy plus ipilimumab and 12.4 months for chemotherapy plus placebo (hazard ratio, 0.91; 95% CI, 0.77 to 1.07; P = .25). Median progression-free survival was 5.6 months for both groups (hazard ratio, 0.87; 95% CI, 0.75 to 1.01). Rates of grade 3 or 4 treatment-related adverse events (TRAEs), any-grade serious TRAEs, and TRAEs leading to discontinuation were numerically higher with chemotherapy plus ipilimumab (51%, 33%, and 28%, respectively) than with chemotherapy plus placebo (35%, 10%, and 7%, respectively). Seven treatment-related deaths occurred with chemotherapy plus ipilimumab, and one occurred with chemotherapy plus placebo. Conclusion The addition of ipilimumab to first-line chemotherapy did not prolong OS compared with chemotherapy alone in patients with advanced squamous NSCLC. The safety profile of chemotherapy plus ipilimumab was consistent with that observed in previous lung and melanoma studies. Ongoing studies are evaluating ipilimumab in combination with nivolumab in this population.

Original languageEnglish
Pages (from-to)3449-3457
Number of pages9
JournalJournal of Clinical Oncology
Volume35
Issue number30
DOIs
StatePublished - Oct 20 2017

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