3080 Polled analysis of nivolumab for the treatment of advanced non-small cell lung cancer and the role of PD-L1 as a biomarker

Abstract

the combination of amrubicin and topoisomerase II inhibitor irinotecan has yet to be examined in randomized clinical trials. We conducted a randomize phase II study to evaluate the efficacy and safety of amrubicin plus irinotecan (AI) compared with cisplatin and irinotecan (CI) in chemonaive patients with extensive-disease (ED) SCLC. Material and Methods: Eligibility criteria included ECOG PS 0−2, age 20 or older, pathologically proven SCLC, ED (Limited disease (LD) with pleural effusion was also eligible), adequate organ function, and written informed consent. Patients were randomized 1:1 to receive either AI (amrubicin 90mg/m on day1 and irinotecan 50mg/m on days 1 and 8 of a 21-day cycle) or CI (cisplatin 60mg/m on day1 and irinotecan 60mg/m on days 1, 8 and 15 of a 28-day cycle). The AI regimen was based on the recommended dose of our previous phase I trial JMTO LC 03−03 (Kawahara M, et al. J Thorac Oncol 2011). The primary endpoint was overall survival (1-year survival rate). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety profile. Stratification factors are PS (0−1 or 2), LDH value (within normal limit or not), institution, and clinical stage (ED or LD with pleural effusion). Results: A total of 100 patients were randomly assigned to AI (n = 50) and to CI (n = 50). One patient was ineligible and excluded from analysis. One-year survival rate was 68.0% (95% confidence interval: 56.2–82.2%) for AI and 62.8% (50.5–78.0%) for CI (one-sided p = 0.29). The stratified log-rank test of two curves comparison showed p = 0.11. Median survival time was 14.7 months for AI and 14.2 months for CI with a hazard ratio (HR) of 0.69. Median PFS was 4.2 months for AI and 5.4 months for CI (stratified log-rank test, p = 0.91). ORR was 70.0% (55.4–82.1%) for AI and 55.1% (40.2–69.3%) for CI (Fisher exact test, p = 0.15). There was no significant difference in hematological toxicity, whereas rates of vomiting, loss of appetite, diarrhea, and elevated serum creatinine are more frequent in CI. Interstitial lung disease (Grade 2 or 3) developed in 5 patients in AI and in 1 patient in CI. There was no treatment-related death. Conclusions: Although the study did not meet its primary endpoint, the combination of amrubicin plus irinotecan showed similar efficacy to that of cisplatin plus irinotecan in chemo-naive patients with ED SCLC. Conflict of interest: Corporate-sponsored Research: Yakult Pharmaceutical Industry.