Ipilimumab—added in a phased regimen to paclitaxel and carboplatin chemotherapy—increased progressionfree survival (PFS) and immune-related PFS in a randomized, double-blind, international, phase 2 study of previously untreated adult patients with non–small-cell lung cancer (NSCLC). However, a concurrent regimen of ipilimumab with the chemo therapy did not differ significantly from a control (placebo plus chemo therapy) regimen (Lynch TJ, et al. J Clin Oncol. 2012; 30:2046-2054. Epub 2012 Apr 30).
Paclitaxel- and carboplatin-induced antigen release occurred before the addition of ipilimumab, which could have contributed to T-cell activation.
To supplement each chemotherapy cycle, patients were randomized to a concurrent ipilimumab regimen (4 ipilimumab doses followed by 2 placebo doses), a phased ipilimumab regimen (2 placebo doses followed by 4 ipilimumab doses), or a control regimen (up to 6 doses of placebo). Ipilimumab or placebo, paclitaxel, and carboplatin were administered intravenously once every 3 weeks for up to 18 weeks, followed by ipilimumab or placebo once every 12 weeks until progression, intolerance, or death. The primary end point was immune-related PFS; PFS and overall survival (OS) periods were key secondary end points.
A total of 204 patients were randomized to the concurrent, phased, or control regimens. Phased ipilimumab significantly improved immune-related PFS compared with the control regimen (P = .05). Phased ipilimumab also improved PFS (P = .02). The differences in favor of phased ipilimumab were greater in patients with squamous histology than in those with non - squamous histology. The concurrent, phased, and control regimens were asso ciated with median OS durations of 9.7, 12.2, and 8.3 months, respectively.
Grades 3 and 4 immune-related adverse event rates were 20%, 15%, and 6% for the concurrent, phased, and control regimens, respectively.
