679 Background: Early tumor shrinkage (ETS) has been reported as an important predictor of favorable outcomes in patients with metastatic colorectal cancer (mCRC) receiving first-line chemotherapy. We investigated the impact of ETS on survival in a randomized phase III study (WJOG4407G), which directly compared mFOLFOX6+bevacizumab (Bev) with FOLFIRI+Bev as first-line treatment. Methods: The subjects of this study were patients with measurable lesions whose tumor responses at 8 weeks were evaluated. ETS was defined as 20% or more decrease in the sum of the longest diameters of target lesions (RECIST ver.1.0) at 8 weeks. Progression-free survival (PFS) and overall survival (OS) were compared between patients with ETS and without ETS in each treatment. Results: Of 402 patients enrolled in the WJOG4407G trial, 354 (mFOLFOX6+Bev/FOLFIRI+Bev 175/179) patients were evaluated for this analysis. In this population, response rate, median PFS, and median OS of mFOLFOX+Bev/FOLFIRI+Bev were 65.7/68.2%, 10.7/12.1 months (HR 0.916, 95%CI 0.725-1.157, p=0.281), and 28.9/31.9 months (HR 0.870, 95%CI 0.653-1.159, p=0.272), respectively. One hundred (57.1%)/113 (63.1%) patients in the FOLFOX+Bev/FOLFIRI+Bev groups achieved ETS. No significant difference of the ratio of the patients with ETS between both groups was observed (p=0.099). In the FOLFIRI+Bev group, both PFS and OS were significantly longer in patients with ETS than those without ETS while there were no remarkable differences in the mFOLFOX6+Bev group (see Table). Conclusions: There were substantial differences in PFS and OS between the patients with and without ETS in the FOLFIRI+Bev group, but not in the FOLFOX+Bev group. The impact of ETS on survival is suggested to be different according to chemotherapy regimens. Clinical trial information: UMIN000001396. [Table: see text]
Trial-level analysis of early tumor shrinkage and disease control rate as intermediate end points of first-line medical treatment in randomized studies of metastatic colorectal cancer
