518MO - Update analysis of the randomized phase II study comparing FOLFIRI plus ramucirumab (RAM) versus FOLFOXIRI plus RAM as first-line treatment for patients with metastatic colorectal cancer: WJOG9216G (RECAST)

Background

We previously reported the results of a randomized phase II study (WJOG9216G) comparing FOLFIRI plus RAM vs. FOLFOXIRI plus RAM for patients with previously untreated metastatic colorectal cancer (Kito et al. ESMO 2022): confirmed objective response rate (ORR, 57.6 vs. 60.3%) and progression-free survival (PFS, median 11.7 vs. 10.5 months) were similar, whereas overall survival (OS) data were immature. A preplanned update analysis was performed.

Methods

Patients were randomly assigned to arm A (FOLFIRI plus RAM) or arm B (8 cycles of FOLFOXIRI plus RAM followed by 5-FU/l-leucovorin plus RAM). Treatment repeated every 2 weeks until disease progression or unacceptable toxicity. Plasma samples were collected at pre-treatment, start of cycle 2, and post-treatment. Sixteen plasma angiogenesis factors were measured by magnetic bead panel Milliplex MAP kits.

Results

From June 2017 to September 2020, 122 patients were randomized (59/63 in arm A/B). Patient characteristics were well-balanced except for liver-limited disease (32/19%). At a median follow-up time of 42.1 months for arm A and 40.4 months for arm B, median OS was 32.6 (95% confidence interval 26.8-36.5) and 28.2 (21.9-31.2) months, respectively (hazard ratio [HR] 1.58, p=0.003). After study treatment, R0 resection (19/11% in arm A/B), radiotherapy (12/16%), and chemotherapy (98/91%) were performed as subsequent treatment. In biomarker analysis combining arm A/B (47/53), there was no relationship between OS and VEGF-D level at pre- and post-treatment, and dynamics during treatment. Patients with high IL-8 level above the median at post-treatment had shorter OS compared with those with low level (29.3 vs. 31.6 months, HR 0.60, p=0.049), and patients with increased heparin-binding EGF-like growth factor (HB-EGF) level from pre-treatment to cycle 2 had longer OS compared with those with decreased level (34.3 vs. 28.2 months, HR 1.78, p=0.024).

Conclusions

WJOG9216 did not show the superiority of FOLFOXIRI plus RAM in terms of OS, ORR, and PFS compared with FOLFIRI plus RAM as first-line treatment for metastatic colorectal cancer.

Clinical trial identification

jRCTs041180166.

Editorial acknowledgement

Legal entity responsible for the study

West Japan Oncology Group (WJOG).

Funding

Eli Lilly Japan K.K.

Disclosure

K. Yamazaki: Financial Interests, Personal, Invited Speaker: Chugai Pharma, Daiichi Sankyo, Yakult Honsha, Takeda, Bayer, Merck Serono, Taiho Pharmaceutical, Lilly, Sanofi, Ono Pharmaceutical, MSD, Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical. Y. Kito: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Ono Pharmaceutical. H. Shoji: Financial Interests, Personal, Advisory Board: Ono Pharmaceutical Co.,Ltd., Zymeworks inc., Astellas; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Institutional, Local PI: Ono Pharmaceutical Co.,Ltd., MSD, Astellas, Amgen, Daiichi Sankyo, AbbVie, AstraZeneca, Taiho Pharmaceutical, Elevation Oncology; Financial Interests, Institutional, Funding: Ono Pharmaceutical Co.,Ltd., Takeda Pharmaceuticals. T. Yamada: Financial Interests, Personal, Invited Speaker: Eli Lilly Japan, Bristol Myers Squibb, Ono Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo. T. Tsushima: Financial Interests, Personal, Invited Speaker: Taiho Pharma, Ono Pharmaceutical, MSD, Bristol Myers Squibb; Financial Interests, Institutional, Local PI: Taiho Pharma, MSD, Ono Pharmaceutical. S. Mitani: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical Co., Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal, Advisory Board: Chugai Pharmaceutical Co.; Financial Interests, Personal, Research Grant: Caris Life Science. 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. H. Hara: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Boehringer Ingelheim, MSD; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, MSD, Ono, Bayer, Chugai, Lilly, Merck Biopharma, Taiho, Takeda, Yakult, Bristol Myers Squibb, Miyarisan; Financial Interests, Institutional, Coordinating PI: Amgen, Astellas, AstraZeneca, Bayel, BeiGene, Chugai, Daiichi Sankyo, Janssen, Merck Biopharma, MSD, Ono, Taiho, ALX Oncology, Jazz Pharmaceuticals. T. Esaki: Financial Interests, Personal, Invited Speaker: Chugai, Taiho, MI Force, Daiichi Sankyo, Eli Lilly, Ono, Bristol; Financial Interests, Institutional, Local PI: MSD, Ono, Nihon Kayaku, IQVIA, Daiichi Sankyo, Chugai, Syneos Health Clinical, Quintiles, Astellas, Astellas Amgen Biopharma, Asahikasei Pharma, Amgen, ALX Oncology, Seagen, Taiho, Jazz Pharmaceuticals Ireland, Bristl. K. Sakai: Financial Interests, Personal, Invited Speaker: Qiagen, Inc., Takeda Pharmaceutical Co., Ltd., Nippon Kayaku Co.,Ltd. K. Nishio: Financial Interests, Personal, Invited Speaker: AstraZeneca K.K., Chugai Pharmaceutical Co.,Ltd., Novartis Pharma K.K., MSD K.K., Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Daiichi Sankyo, Invitae Japan, Nichirei Biosciences Inc., Maruho Co., Ltd.; Financial Interests, Personal, Advisory Board: Otsuka Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Limited., Guardant Health Inc., Janssen Pharmaceutical; Financial Interests, Personal, Research Grant: West Japan Oncology Group, Nichirei Biosciences Inc., Hitachi, Ltd., Osakaminami Hospital, Sysmex Corporation, Otsuka Pharmaceutical, Thoracic Oncology Research Group, University Public Corporation Osaka.. H. Kawakami: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb Co. Ltd., Ono Pharmaceutical Co. Ltd, Daiichi Sankyo Co. Ltd., Bayer Yakuhin Ltd, Eli Lilly Japan K.K., MSD K.K., Chugai Pharmaceutical Co. Ltd., Merck Biopharma Co., Ltd., Takeda Pharmaceutical Co. Ltd., Yakult Pharmaceutical Industry, Teijin Pharma Ltd., Taiho Pharmaceutical Co. Ltd.; Financial Interests, Personal, Advisory Board: Daiichi Sankyo Co. Ltd., Astellas; Financial Interests, Personal, Other, Lecture: GSK K.K, Otsuka Pharmaceutical Co., Ltd.; Financial Interests, Institutional, Research Grant, Investigator-Initiated Trial: Bristol Myers Squibb Co. Ltd.; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical Co. Ltd, Eisai Co., Ltd., Kobayashi Pharmaceutical Co. Ltd., Parexel International Corp., Pra Healthsciences, EPS Corporation., Kissei Pharmaceutical Co., Ltd., EPS International Co.,Ltd,., MSD K.K., Ono Pharmaceutical Co.,Ltd., PPD-SNBL K.K, SymBio Pharmaceuticals Limited., IQVIA Services Japan K.K., Syneos Health Clinical K.K., Nippon Kayaku Co.,Ltd., EP-CRSU Co., Ltd., Mebix, Inc., Bristol-Myers Squibb K.K., Janssen Pharmaceutical K.K., Eisai Co., Ltd., AstraZeneca K.K., Mochida Pharmaceutical Co., Ltd., Covance Japan Inc., Japan Clinical Research Operations, Chugai Pharmaceutical Co.,Ltd., Takeda Pharmaceutical Co.,Ltd., GSK K.K., Sanofi K.K., Nippon Boehringer Ingelheim Co.,Ltd., Sysmex Corporation, Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., SRL, Inc., Daiichi Sankyo Co., Ltd., Amgen Inc., Medical Reserch Support, Eli Lilly Japan K.K.. S. Hironaka: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Other, lecture: Ono Pharmaceutical, BMS, Eli Lilly, Taiho, Daiichi Sankyo, MSD, Chugai, Merck Biopharma, Takeda, Yakult Honsha, Bayer, Novartis, Nihon Servier. K. Muro: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Ono, Chugai, Astellas; Financial Interests, Personal, Invited Speaker: Eli Lilly, Ono, Daiichi Sankyo, Taiho, Bristol-Myers Squibb, Takeda, MSD; Financial Interests, Institutional, Research Grant, Including local PI as role: Astellas, Amgen, Sanofi, Daiichi Sankyo, Taiho, MSD, Pfizer, Merck Biopharma, Eisai, Ono, Novartis, PRA Health Sciences Inc., Parexel International Inc.; Financial Interests, Personal, Steering Committee Member: Chugai, AstraZeneca, Amgen; Non-Financial Interests, Principal Investigator: Takeda. All other authors have declared no conflicts of interest.