(ChemotherapyAdvisor) – Phased ipilimumab plus paclitaxel and carboplatin improved immune-related progression-free survival (PFS) and PFS in patients with stage IIIB/IV non–small-cell lung cancer (NSCLC), supporting additional investigation in this population, a study in the Journal of Clinical Oncology online April 30 has found.
Previously, ipilimumab, an anticytotoxic T-cell lymphocyte-4 monoclonal antibody, has shown a survival benefit in melanoma, with adverse events (AEs) managed by protocol-defined guidelines, the investigators noted.
In this Phase 2 study, 204 patients with chemotherapy-naive NSCLC were randomly assigned 1:1:1 to receive paclitaxel 175mg/m2 and carboplatin (AUC, 6) with either placebo (control) or ipilimumab in one of two regimens: concurrent ipilimumab, which comprised 4 doses of ipilimumab plus paclitaxel and carboplatin followed by 2 doses of placebo plus paclitaxel and carboplatin, or phased ipilimumab, comprised of 2 doses of placebo plus paclitaxel and carboplatin followed by 4 doses of ipilimumab plus paclitaxel and carboplatin.
Treatment was administered intravenously every 3 weeks for ≤18 weeks as induction, with eligible patients continuing ipilimumab or placebo every 12 weeks as maintenance therapy.
The study met its primary end point of improved immune-response PFS for phased ipilimumab vs the control (HR, 0.72; P=0.05), but not for concurrent ipilimumab (HR 0.81; P =0.13). “Phased ipilimumab also improved PFS according to modified WHO criteria (HR 0.69; P=0.02),” the investigators wrote.
Phased ipilimumab was associated with a median immune-response PFS of 5.7 months; concurrent ipilimumab, 5.5 months; and control, 4.6 months. Median PFS was 5.1, 4.1, and 4.2 months, respectively. Immune-related best overall response rate was 32% in the phased ipilimumab group, 21% in the concurrent ipilimumab group, and 18% in the control group. Best overall response rate was 32%, 21% and 14%, respectively; median overall survival was 12.2, 9.7, and 8.3 months.
Overall rates of grade 3 and 4 immune-related adverse events were 15% for phased ipilimumab, 20% concurrent ipilimumab, and 6% for the control group. Two patients died from treatment-related toxicity, 1 each in the concurrent and control groups.
“…these results provide justification for additional investigation of ipilimumab in combination with chemotherapy in patients with NSCLC,” the investigators concluded.