Phase I Trial of MK-3475 and Concurrent Radiation for the Elimination of Extensive-Stage Small Cell Lung Cancer

We present toxicity and efficacy findings from a phase I trial that combines MK-3475 with concurrent radiation therapy in patients with extensive stage small-cell lung cancer (ES-SCLC). Eligible patients with ES-SCLC after completion of standard chemotherapy were enrolled in a nonrandomized fashion to receive consolidation radiation therapy. Maximum tolerated dose (MTD) of MK-3475 was determined with a 3 + 3 dose escalation design, starting at 100 mg and either decreased to 70 mg or increased to 150 mg, then 200 mg. MK-3475 q3w) for up to 16 cycles. Radiation therapy was delivered to the chest 45 Gy in 15 fractions (3 Gy /fraction given daily. Toxicity was scored per the Common Terminology Criteria for Adverse Events version 4.0 and was evaluated by radiation and medical oncologists. Disease response was scored per immunotherapy related response criteria by a radiologist. Kaplan-Meier method and log-rank test were used to assess progression-free survival (PFS) and overall survival (OS). Thirty-five patients were enrolled; of these, one was not financially cleared, one failed screening, another was non-compliant and two were removed due to toxicity. In all, 25 patients completed radiation therapy. MK-3475 was tolerated and dose was escalated up to MTD of 200 mg. The median number of MK-3475 cycles was 4 (range 1-16). One patient completed all 16 cycles of MK-3475. Four patients received prophylactic cranial irradiation (PCI). To date, 22 patients were taken off the trial; 2 due to toxicity, 1 due to non-adherence, and 19 due to disease progression. Median follow-up was 7.2 months (range 1.1-12.7 months). No treatment related grade 4 toxicities were observed; there were three grade 3 events in 1 (3%) patient possibly related to treatment (paresthesia and myasthenia) and one grade 3 event probably or definitely related to treatment (rash). None of these adverse events were in the field of radiation. Of the 24 patients with evaluable imaging data, 1 (4%) had CR, 1 (4%) had PR, 8 (33%) had SD, and 13 (54%) had PD as best responses. Median follow-up was 6 months (range 1-12 months) at the time this abstract was written. Median PFS and OS were 4.6 and 8.4 months, respectively. These data suggest that the addition of concurrent and radiation therapy have acceptable toxicity profiles for ES-SCLC. Our short-term outcomes are comparable to historic controls using only consolidative RT in ES-SCLC. Further follow-up is needed to assess long-term outcomes.