Ipilimumab, an anti-CTLA4 monoclonal antibody, demonstrated survival benefit in melanoma
with immune-related (ir) adverse events (irAEs) managed by the protocol-defined guidelines.
This phase 2 study evaluated ipilimumab+paclitaxel (Taxol)/carboplatin in extensive-disease-small-cell
lung cancer (ED-SCLC).
Patients (n=130) with chemotherapy-naïve ED-SCLC were randomized 1: 1: 1 to receive
paclitaxel (175 mg/m2)/carboplatin (area under the curve=6) with either placebo (control)
or ipilimumab 10 mg/kg in two alternative regimens, concurrent ipilimumab (ipilimumab+paclitaxel/carboplatin
followed by placebo+paclitaxel/carboplatin) or phased ipilimumab (placebo+paclitaxel/carboplatin
followed by ipilimumab+paclitaxel/carboplatin). Treatment was administered every 3
weeks for a maximum of 18 weeks (induction), followed by maintenance ipilimumab or
placebo every 12 weeks. End points included progression-free survival (PFS), irPFS,
best overall response rate (BORR); irBORR, overall survival (OS), and safety.
Phased ipilimumab, but not concurrent ipilimumab, improved irPFS versus control [HR
(hazard ratio)=0.64; P=0.03]. No improvement in PFS (HR=0.93; P=0.37) or OS (HR=0.75;
P=0.13) occurred. Phased ipilimumab, concurrent ipilimumab and control, respectively,
were associated with median irPFS of 6.4, 5.7 and 5.3 months; median PFS of 5.2, 3.9
and 5.2 months; median OS of 12.9, 9.1 and 9.9 months. Overall rates of grade 3/4
irAEs were 17, 21 and 9% for phased ipilimumab, concurrent ipilimumab and control,
These results suggest further investigation of ipilimumab in ED-SCLC.