EXPERIENCE OF APPLICATION OF IPILIMUMAB IN COMBINED THERAPY OF SMALL-CELL LUNG CANCER. ANALYSIS OF DATA OF THE MULTICENTER RANDOMIZED RESEARCH CA 184-156, PHASE III

Abstract

Patients with advanced small cell lung cancer (SCLC) have an extremely poor prognosis against a background of standard therapy with a combination of etoposide with platinum drugs. In a randomized, double-blind of the CA184-156 phase 3, the efficacy and safety of ipilimumab or placebo in combination with etoposide and platinum preparations was evaluated as the first line treatment for disseminated SCLC. Material and methods. Randomization of patients was carried out in a ratio of 1:1 in the group of therapy: etoposide + platinum drug (carboplatin or cisplatin) + ipilimumab and etoposide + platinum preparation + placebo. Ipilimumab/placebo was administered at a dose of 10 mg/kg every 3 weeks, starting from the 3rd course of chemotherapy to the 6th course of chemotherapy. Further, in the absence of progression, maintenance therapy with ipilimumab/placebo was performed every 12 weeks. The main end point of the study was the assessment of overall survival (OS). Results. Out of 1,132 randomized patients, 954 received at least 1 administration of ipilimumab/placebo in combination with chemotherapy: ipilimumab, n = 478; placebo, n = 476. Median OS was 11.0 months in the chemotherapy group with ipilimumab and 10.9 months, in the chemotherapy group with placebo (RR, 0.94, 95% CI, 0.81-1.09, p =0,3775). The median progression-free survival was 4.6 months in the chemotherapy group with ipilimumab and 4.4 months in the chemotherapy group with placebo. (RR, 0.85, 95% CI, 0.75-0.97). The frequency and severity of side effects in the compared groups was similar, with the exception of diarrhea, rash, and colitis, which occurred significantly more frequent in the chemotherapy group with ipilimumab. The frequency of the discontinuation of therapy due to toxicity was higher in the chemotherapy group with ipilimumab (18% vs. 2%). Treatment-related deaths accounted for 5 in the chemotherapy group with ipilimumab and 2 - in the chemotherapy group with placebo. Conclusion. The addition of ipilimumab to chemotherapy did not contribute to an increase in OS in comparison with only chemotherapy in advanced SCLC patients. Unexpected adverse events in the chemotherapy group with ipilimumab were not noted. The study of the efficacy of ipilimumab in patients with disseminated SCLC in combination with PD1 inhibitors is ongoing. The results obtained in the analysis of data in a subset of 33 patients who participated in this study on the basis of the Department chemotherapy of N.N. Blokhin Russian Cancer Research Center, correspond to data obtained in the entire multicenter study CA184-156.