Ramucirumab (Rmab), an anti-VEGFR-2 antibody, inhibits VEGF-A, -C, -D binding and endothelial cell proliferation, although bevacizumab binds to and blocks circulating VEGF-A. We had presented the result of dose finding phase Ib study of FOLFOXIRI plus Rmab for metastatic colorectal cancer (mCRC) patients (pts) in the 19th World Congress on Gastrointestinal Cancer. Here we reported the update analysis.
The eligibility criteria included pts with unresectable colorectal adenocarcinoma, 20-75 years, ECOG PS 0-1 (pts > 70 years were eligible if their ECOG PS was 0), wild-type or heterozygous UGT1A1 *28 or *6, no history of prior chemotherapy, and adequate organ function. Three dose levels were planned as follows: oxaliplatin and Rmab dose was fixed at 85 mg/m2 and 8 mg/kg, respectively. Level 1: 5-fluorouracil (5-FU) 3200 mg/m2, irinotecan (IRI) 165 mg/m2, Level 0 as starting dose: 5-FU 2400 mg/m2, IRI 150 mg/m2, and Level -1: 5-FU 2400 mg/m2, IRI 120 mg/m2. The dose-limiting toxicity (DLT) was evaluated in the first cycle.
We enrolled a total of 10 pts (4 pts in the Level 0 and 6 pts in the Level 1). The pts characteristics were as follows: median age, 64 (range, 44-68); male/female, 6/4; ECOG PS 0/1, 8/2; RAS wild/mutant, 1/9; UGT1A1 *1*1/*1*28, 4/6. One patient was excluded for the DLT evaluation due to lack of safety evaluation on cycle 1 day 8. No DLT was observed in the 9 DLT-evaluable pts. Among 8 pts who had at least one tumor evaluation, early tumor shrinkage, response rate and disease control rate was 87.5%, 75% and 100%, respectively. In the first 3-cycle, major adverse events were Grade (G) 4 neutropenia (n = 2), G3 neutropenia (n = 1), G3 hypertension (n = 2), G2 thrombocytopenia (n = 4), G2 anorexia (n = 3), G2 hypertension (n = 3), G2 fatigue (n = 2) and G2 proteinurea (n = 2). G-CSF was administered in 2 pts in the first cycle.
FOLFOXIRI plus Rmab showed a promising antitumor activity with acceptable toxicity, although this study had a small sample size. A randomized phase II study of FOLFIRI plus Rmab versus FOLFOXIRI plus Rmab (Level 1) for chemotherapy-naïve mCRC pts (WJOG9216G trial; UMIN000026527) is on-going.
Clinical trial identification
Legal entity responsible for the study
Shizuoka Cancer Center
Shizuoka Cancer Center
All authors have declared no conflicts of interest.