P-107 Efficacy of 2nd-line ramucirumab (RAM) plus FOLFIRI for RAS wild-type metastatic colorectal cancer (mCRC) by prior regimen: Subgroup analysis of the JACCRO CC-16

Abstract

There have been few studies which prospectively evaluated the efficacy and safety of RAM plus FOLFIRI after 1st-line anti-EGFR antibody-containing therapy in RAS wild-type mCRC. We therefore conducted a multicenter phase 2 trial, JACCRO CC-16, and reported 6month-PFS rate of 58.2 % and median PFS of 7.0 months. The JACCRO CC-16 was a single arm, phase 2 trial to evaluate the efficacy and safety of RAM (8 mg/kg) plus FOLFIRI (irinotecan 150 mg/m2, bolus 5-FU 400 mg/m2, infusional 5-FU 2400 mg/m2) in mCRC patients with RAS wild-type tumors and ECOG PS 0 or 1, after 1st-line oxaliplatin-based doublet (Ox-doublet) or triplet plus anti-EGFR antibody. Primary endpoint was 6month-PFS rate. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), early tumor shrinkage (ETS), and overall survival. The subgroup post-hoc analysis was performed to investigate the differences in clinical outcomes of RAM plus FOLFIRI according to previous 1st-line regimen, doublet or triplet. A total of 92 patients were enrolled between October 2018 and 2020 December. Ninety-one patients were analyzed as the full analysis set. In prior 1st-line treatment, 19 (21%) patients were treated with modified-FOLFOXIRI plus cetuximab, and 72 (79%) patients were treated with doublet plus anti-EGFR antibody. The doublet group included 3 patients who failed to achieve an ETS during 1st-line treatment. The 6months-PFS rate (95% CI) was 57.9 % (33.2 to 76.3) in the triplet group and 58.3 % (46.1 to 68.7) in the doublet group. The PFS was significantly longer in the doublet group (median PFS, 7.4 months, 95% CI 5.7 to 9.0) compared to the triplet group (median PFS, 6.4 months, 95% CI 3.8 to 7.35) (p = 0.036, log-rank test). The ORR and DCR were 5.6 % and 94.4 % in the triplet group and 12.1 % and 84.8 % in the doublet group, with no significant difference between 2 groups (p = 0.42 and p = 0.28, respectively). This study demonstrated a favorable efficacy of FOLFIRI plus RAM treatment in RAS wild-type mCRC patients treated with 1st-line anti-EGFR antibody-containing therapy. It may also achieve a certain effect in cases previously treated with triplet-based regimen.