Phased, but not concurrent ipilimumab plus paclitaxel and carboplatin improves NSCLC outcome.

  • Major finding: Phased, but not concurrent ipilimumab plus paclitaxel and carboplatin improves NSCLC outcome.

  • Concept: Chemotherapy-induced antigen release prior to ipilimumab treatment may increase efficacy.

  • Impact: The sequence of chemotherapy and immunotherapy administration affects outcome in NSCLC.

Ipilimumab, a monoclonal antibody that blocks the binding of cytotoxic T-cell lymphocyte-4 (CTLA-4) to its ligands and augments antitumor T-cell responses, has previously been shown to improve overall survival in patients with metastatic melanoma. Preclinical studies have suggested that cytotoxic agents such as taxanes and platinum-based compounds may potentiate ipilimumab activity and promote T-cell–mediated responses to tumor-specific antigens released by dying tumor cells. Based on these clinical and preclinical findings, Lynch and colleagues conducted a randomized, double-blind, international, multicenter phase II study to determine whether ipilimumab is also effective in non–small cell lung cancer (NSCLC) in combination with paclitaxel and carboplatin, a common first-line treatment for NSCLC. Previously untreated NSCLC patients were randomly assigned to receive paclitaxel and carboplatin plus either placebo or ipilimumab in either a concurrent regimen or a phased regimen in which several doses of paclitaxel and carboplatin were given prior to ipilimumab, with the rationale that antigen release and T-cell activation would presumably occur before ipilimumab treatment. Phased ipilimumab improved immune-related progression-free survival to 5.7 months compared with 5.5 months for concurrent ipilimumab and 4.6 months for placebo. Phased ipilimumab also increased the median overall survival compared with concurrent ipilimumab and placebo (12.2, 9.7, and 8.3 months, respectively). The most common adverse events were typically those associated with paclitaxel and carboplatin, and immune-related adverse events were similar to those observed in previous ipilimumab clinical trials. Collectively, these findings suggest that the use of chemotherapy prior to anti–CTLA-4 immunotherapy may improve clinical outcome and indicate that further studies of ipilimumab in combination with chemotherapy are warranted in NSCLC.

Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, et al. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non–small cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol 2012 Apr 30 [Epub ahead of print].

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