Phase III Trial of Ipilimumab Combined With Paclitaxel and Carboplatin in Advanced Squamous Non–Small-Cell Lung Cancer

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.

The role and therapeutic implications of T cells in cancer of the lung

“…55 More promisingly, a double-blinded phase-III trial investigated the addition of pembrolizumab to chemotherapy (pemetrexed and a platinum-based chemotherapy viz. 55 More promisingly, a double-blinded phase-III trial investigated the addition of pembrolizumab to chemotherapy (pemetrexed and a platinum-based chemotherapy viz.…”

Immunotherapy and Immunoprofylaxis for Cancer Patients: Paradigm Shift

“…Результаты приведенного исследования не отличались от всех предыдущих без применения ипилимумаба, где 2-летняя общая выживаемость колебалась от 10 до 20% [2][3][4]. Сходная тенденция отмечена в другом рандомизи-рованном исследовании с участием 749 пациен-тов с немелкоклеточным раком легкого, получав-ших ипилимумаб в комбинации с паклитакселом и карбоплатином [5]. В исследовании не было достигнуто существенной разницы в показателях общей выживаемости основной группы по сравне-нию с группой, получавшей только химиотерапию.…”

Erratum: The efficacy and safety of anti‐PD‐1/PD‐L1 antibodies combined with chemotherapy or CTLA4 antibody as a first‐line treatment for advanced lung cancer

“…The correct citation and reference is “Govindan R, Szczesna A, Ahn MJ, et al Phase III Trial of ipilimumab combined with paclitaxel and carboplatin in advanced squamous non‐small‐cell lung cancer. J Clin Oncol 2017; 35: 3449–57.”…”