525P - Final analysis of the JACCRO CC-16: Ramucirumab plus FOLFIRI for RAS wild-type mCRC refractory to anti-EGFR antibody

Background

There have been few studies which prospectively evaluated the efficacy and safety of FOLFIRI plus anti-VEGF inhibitor after anti-EGFR antibody containing chemotherapy in RAS wild-type metastatic colorectal cancer (mCRC). We therefore conducted the JACCRO CC-16 trial which investigated the clinical outcomes of 2nd-line ramucirumab (RAM) plus FOLFIRI after initial anti-EGFR antibody containing regimen in patients with RAS wild-type mCRC, and have reported favorable outcomes (ESMO Open 2023;8(5):101636).

Methods

JACCRO CC-16 was a multicenter, phase 2 trial with primary endpoint of 6-month PFS rate and secondary endpoints of PFS, overall survival (OS), objective response rate (ORR), early tumor shrinkage (ETS) rate, and safety. A total of 92 patients were enrolled between October 2018 and December 2020. Here, we performed a final analysis using January 2024 as the data cutoff.

Results

Ninety-one patients were evaluable: primary site left/right 86/4, initial doublet/triplet regimen 72/19. Median follow-up time was 46.0 months. The 6-month PFS rate was 58.2% (90% CI; 49.3-66.2) with 89 events (97.8%). The median PFS was 7.0 months (95% CI; 5.7-7.6), and the median OS was 21.4 months (95% CI; 16.5-26.3). In 83 evaluable patients for ETS, 14 (16.9 %) patients achieved ETS. The median PFS were 9.8 months (95%CI, 5.7-18.5) in the ETS positive (+) versus 6.4 months in the ETS negative (-) (HR 0.55, p=0.04). The median OS was 33.5 months in the ETS+ versus 17.6 months in the ETS- (HR 0.39, p=0.0065). A post-hoc analysis showed that median PFS was significantly longer in the initial doublet regimen group compared to the triplet group: 7.5 months versus 6.4 months (HR 0.55, p=0.026). However, median OS was comparable between the 2 groups: 21.3 months versus 25.0 months.

Conclusions

After long follow-up time, RAM plus FOLFIRI had favorable activity as 2nd-line treatment after anti-EGFR antibody in combination with doublet or triplet chemotherapy in RAS wild-type mCRC patients. The ETS may predict longer survival time of 2nd-line treatment with RAM plus FOLFIRI.

Clinical trial identification

jRCTs061180002.

Editorial acknowledgement

Legal entity responsible for the study

Non-Profit Organization Japan Clinical Cancer Research Organization.

Funding

Eli Lilly Japan K.K.

Disclosure

H. Yasui: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Chugai Pharma, Bristol-Myers Squibb, Daiichi-Sankyo, Terumo, Eli Lilly Japan, Merck Biopharma, Yakult Honsha, Bayer Yakuhin, Takeda Pharmaceutical; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical; Financial Interests, Institutional, Local PI: MSD, Daiichi-Sankyo, Ono Pharmaceutical, Astellas Pharma, Amgen, AstraZeneca. M. Nakamura: Financial Interests, Personal, Invited Speaker: Bayer Yakuhin, Ltd, Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eli Lilly Japan K.K., Merck Biopharma Co., Ltd., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Yakult Honsha Co., Ltd., Merck & Co., Servier. K. Kataoka: Financial Interests, Personal, Invited Speaker: Merck Biopharma, Eli Lilly. M. Shiozawa: Financial Interests, Personal, Invited Speaker: Lilly Japan, Merck Serono, Taiho Pharmaceutical, Yakult Honsha, Takeda, Ono Pharmaceutical, Johnson & Johnson, Kaken. Y. Sunakawa: Financial Interests, Personal, Invited Speaker: Eli Lilly Japan K.K., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Daiichi Sankyo Co., Ltd., Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal, Advisory Board: Merck Biopharma Co., Ltd.; Financial Interests, Personal and Institutional, Research Grant: Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Parexel International Inc., IQVIA, Ono Pharmaceutical Co., Ltd., CMIC Shift Zero K.K., PRA Health Sciences, AMGEN; Non-Financial Interests, Project Lead: Japan Clinical Cancer Research Organization. M. Kotaka: Financial Interests, Personal, Invited Speaker: Chugai, Takeda. H. Okuyama: Financial Interests, Personal, Invited Speaker: Incyte, Novartis, Taiho Pharmaceutical, Chugai pharmaceutical, AstraZeneca, Guardant Health Japan; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Institutional, Local PI: Hutchison Medipharma. W. Ichikawa: Financial Interests, Personal, Invited Speaker: Merck BioPharma, Bristol Myers Squibb, Chugai Pharmaceutical, Yakult Honsha, AstraZeneca, Daiichi Sankyo, Taiho Pharmaceutical, MSD, Eli Lilly Japan; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo, Shionogi. A. Tsuji: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., MSD Corporation, Daiichi Sankyo Co., Ltd., Bristol Myers Squibb, Merck Biopharma Co., Ltd.; Financial Interests, Personal, Local PI: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.