O1-21-6 - A Phase III Study of Cddp, Etop and Irinotecan Vs. Topotecan as 2Nd-Line Chemotherapy for Sensitive Relapsed Sclc: Jcog0605

Abstract

Background: ETOP and irinotecan are drugs known to exert promising activity in SCLC. A phase II study of weekly chemotherapy using a combination of CDDP, ETOP and irinotecan (PEI), which are known to inhibit both topoisomerase I and II, showed quite favorable outcome in patients with sensitive relapsed SCLC (response rate 78%, median survival time 11.8 months, 1-year survival 49%). A phase III study confirming the superiority of PEI over topotecan as second-line chemotherapy in patients with sensitive relapsed SCLC was therefore conducted.Methods: SCLC patients who responded to first-line treatment and relapsed/progressed more than 90 days after the completion of first-line treatment were eligible for this study. Additional eligibility criteria included age 20-75 years, PS of 0-2, and adequate organ functions. Patients were randomized 1:1 to PEI, which consisted of CDDP (25 mg/m2) weekly for 10 weeks, ETOP (60 mg/m2) for 3 days on weeks 1, 3, 5, 7, and 9, and irinotecan (90 mg/m2) on weeks 2, 4, 6, 8 and 10 with granulocyte colony-stimulating factor support, or to topotecan (1.0 mg/m2) on days 1-5, every 3 weeks for 4 courses. The primary endpoint was overall survival. The planned sample size was 180 patients, to attain 80% power with a one-sided alpha of 5%.Results: From Sep. 2007 to Nov. 2012, 180 patients were randomized to topotecan (n = 90) and PEI (n = 90): median age 64 (44-75) years; M/F 155/25; LD/ED 45/135; PS 0-1/2 175/5. The overall survival was significantly longer in the PEI arm than in the topotecan arm (HR 0.67; 90% CI 0.51-0.88; p = 0.0079) with MST 18.2 months vs. 12.5 months. PFS was also significantly longer in the PEI arm (HR 0.50; 95% CI 0.37-0.68; p < 0.0001) with the median PFS 5.7 months vs. 3.6 months. Grade 3/4 adverse events in PEI and topotecan arms, respectively, were: neutropenia 83.3% vs. 85.6%; anemia 84.4% vs. 27.8%; thrombocytopenia 41.1% vs. 27.8%; diarrhea 7.8% vs. 0%; febrile neutropenia 31.1% vs. 6.7%. There was 1 treatment-related death in the PEI arm, and 2 in the topotecan arm.Conclusions: The combination chemotherapy with CDDP, ETOP and irinotecan should be considered as the standard second-line chemotherapy for sensitive relapsed SCLC.