Randomized phase III study of irinotecan (CPT-11) versus weekly paclitaxel (wPTX) for advanced gastric cancer (AGC) refractory to combination chemotherapy (CT) of fluoropyrimidine plus platinum (FP): WJOG4007 trial.

Abstract

4002 Background: A combination CT of FP has been regarded as the standard first-line treatment for AGC. Although two randomized trials showed a survival benefit of second-line CT (CPT-11 or docetaxel) compared with best supportive care, no standard regimen has been established. In Japan, wPTX has been used more frequently than docetaxel as the second‑line CT. The objective of this study was to compare CPT-11 with wPTX in patients (pts) with AGC refractory to FP. Methods: Patients with AGC refractory to the first‑line FP regimen were randomized 1:1 to either CPT-11 (150 mg/m2, q2w) or wPTX (80 mg/m2, days 1, 8, 15, q4w). The primary endpoint was overall survival (OS) and secondary endpoints were progression‑free survival (PFS), overall response rate (ORR), adverse events and receiving rates of third-line CT. To demonstrate an increase in median OS from 5 months (wPTX) to 7.5 months (CPT-11) with 2-sided alpha 5% and 80% power, 220 pts were required. Results: Between Aug 2007 and Aug 2010, 223 pts were enrolled; 112 pts were randomized to CPT-11 and 111 pts to wPTX. Baseline characteristics were well balanced between arms. Median OS was 8.4 months for CPT-11 and 9.5 months for wPTX (HR 1.132; 95% CI, 0.86-1.49; p=0.38). Median PFS was 2.3 months for CPT-11 and 3.6 months for wPTX (HR 1.14; 95% CI, 0.88-1.49; p=0.33). The ORR was 13.6% (12/88) for CPT-11 and 20.9% (19/91) for wPTX (p=0.20). The most common grade 3/4 adverse events were neutropenia (39.1% for CPT-11 vs. 28.7% for wPTX), anemia (30.0% vs. 21.3%), anorexia (17.3% vs. 7.4%) and fatigue (12.7% vs. 6.5%). Four (4%) CPT-11 and three (3%) wPTX recipients died within 30 days after the last administration. Subsequent CT was performed in 80 pts (71%) for CPT-11 and 97 pts (89%) for wPTX. Seventy-five pts (67%) in the CPT-11 group and 87 pts (80%) in the wPTX group received the crossover CT. Conclusions: The WJOG4007 trial, the first phase III study comparing second-line CT regimens for AGC, did not demonstrate the superiority of CPT-11 over wPTX. Thus, wPTX can be adopted as a control arm of future phase III trials of second-line CT for AGC.