389P Randomized phase II study of FOLFIRI plus ramucirumab versus FOLFOXIRI plus ramucirumab as first-line treatment for metastatic colorectal cancer: WJOG9216G (RECAST)

Abstract

FOLFIRI plus bevacizumab (BEV) is widely used as first-line treatment for metastatic colorectal cancer (mCRC), and FOLFOXIRI plus BEV is an option. Clinical outcomes of ramucirumab (RAM) combined with FOLFIRI and FOLFOXIRI in first-line treatment are not well known. We conducted a randomized phase II study to assess the superiority of FOLFOXIRI plus RAM over FOLFIRI plus RAM as first-line treatment for mCRC. Main eligibility criteria were unresectable colorectal adenocarcinoma, age 20-75 years, ECOG PS <1, no previous chemotherapy, measurable lesions, and wild-type or heterozygous UGT1A1 *28/*6. In arm A, patients received FOLFIRI (irinotecan [IRI] 180 mg/m2, l-leucovorin [l-LV] 200 mg/m2, bolus 5-fluorouracil [5-FU] 400 mg/m2, continuous 5-FU 2400 mg/m2) plus RAM (8 mg/kg) biweekly until disease progression. In arm B, patients received 8 cycles of FOLFOXIRI (oxaliplatin 85 mg/m2, IRI 165 mg/m2, l-LV 200 mg/m2, continuous 5-FU 3200 mg/m2) plus RAM biweekly followed by 5-FU/l-LV plus RAM. The primary endpoint was confirmed objective response rate (ORR). The sample size was 120, assuming ORRs of 50/70% in arm A/B with 80% power at a 10% α-level (one-sided). A total of 122 patients were randomized (59/63 in arm A/B) from Jun 2017 to Sep 2020. The baseline characteristics in arm A/B were as follows: median age 64/65, male 66/70%, right colon 29/30%, RAS mutant 61/67%, BRAF mutant 9/3%, liver-limited disease 32/19%. 50/51 (84.7/81.0%) patients in arm A/B completed 8 cycles. The ORRs in arm A/B were 57.6/60.3% (odds ratio 1.11, p=0.76). With median follow-up of 27.4/25.3 months in arm A/B, median progression free survival (PFS) was 11.7/10.5 months (hazard ratio 1.13, p=0.57). R0 resection was performed in 10/6 (16.9/9.5%) patients in arm A/B. Major grade >3 adverse events (incidence in arm A/B) were neutropenia (44.1/72.6%), hypertension (15.3/19.4%), proteinuria (13.6/12.9%), anorexia (3.4/14.5%), febrile neutropenia (3.4/11.3%), and diarrhea (1.7/8.1%). FOLFOXIRI plus RAM did not show significant superiority in terms of ORRs and PFS compared with FOLFIRI plus RAM as first-line treatment for mCRC.