Update on JACCRO CC-11 trial of 1st-line modified-FOLFOXIRI plus bevacizumab for RAS mutant metastatic colorectal cancer

Abstract

Abstract Background FOLFOXIRI plus bevacizumab (bev) is one of preferred 1st-line regimens for RAS mutant metastatic colorectal cancer (mCRC); however, the original dosage is slightly toxic for Japanese patients (pts) due to frequent febrile neutropenia. We have reported that modified (m)-FOLFOXIRI (IRI 150mg/m2, OHP 85mg/m2, levofolinate 200mg/m2, and 5-FU 2400mg/m2 for 46-h continuous, up to 12 cycles followed by maintenance with 5-FU/levofolinate) plus bev has good objective response rate (ORR) of 76% as well as tolerability in Japanese pts with RAS mutant mCRC [Satake H, et al. Oncotarget 2018]. However, the follow-up time was short; therefore, clinical data was immature. Methods The primary endpoint was ORR. Progression-free survival (PFS), overall survival (OS), early tumor shrinkage (ETS), depth of response (DpR), and safety were secondary endpoints. The tumor shrinkage was evaluated every 8 weeks by the external review board. Pre-planned updated analysis was performed in January 2019. Results 62 pts (median 62.5-y old, 92% PS0, 90%/10% for KRAS/NRAS mutations, 27% right-side) were evaluable for efficacy and 63 pts for toxicity. The median cycle of treatment was 15 (range 1-46). Two pts still continued the protocol treatment and 40 (67%) pts received 2nd-line chemotherapy (triplet-regimen 28%, IRI-regimen+bev 23%, FOLFIRI+ramucirumab 15%, FOLFIRI+aflibercept 3%, OHP-regimen 10%, 5-FU+bev 10%, FTD/TPI 10%). Fourteen (23%) pts underwent surgery after protocol treatment. Median PFS was 11.9 (95%CI 9.5-14.0) months, median OS was 31.2 (95%CI 25.8-37.6), ETS was 73.8%, and median DpR was 49.2% (-28.7-100). Sub-analyses in each tumor side showed that ETS, DpR, median OS were 77.3%, 49.6%, 34.0 months in the left-side and 64.7%, 40.2%, 26.2 months in the right-side. No new adverse events were observed. Conclusions Updated analysis of the JACCRO CC-11 trial shows that m-FOLFOXIRI plus bev is a clinically useful regimen as a good option for RAS mutant mCRC.