Abstract 389P
Background
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.
Methods
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).
Results
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%).
Conclusions
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.
Clinical trial identification
jRCTs041180166.
Editorial acknowledgement
Legal entity responsible for the study
West Japan Oncology Group.
Funding
Eli Lilly.
Disclosure
Y. Kito: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Daiichi Sankyo. 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. H. Shoji: Other, Institutional, Other, Research fund: ONO Pharmaceuticals, Astellas, MSD, Takeda, Amgen. T. Yamada: Financial Interests, Personal, Speaker’s Bureau, outside the submitted work: Ono Pharmaceutical Co, Chugai Pharmaceutical Co, Merck Serono, Eli Lilly, Daiichi Sankyo, Yakult Honsha Co. Ltd., Taiho Pharmaceutical Co. Ltd.. T. Tsushima: Financial Interests, Personal, Invited Speaker: Eli Lilly Japan, Takeda, Taiho Pharma, Ono Pharmaceutical, MSD; Financial Interests, Institutional, Invited Speaker: Taiho Pharma, MSD, Ono Pharmaceutical, BeiGene, Chugai Pharmaceutical. S. Mitani: Financial Interests, Personal, Advisory Board: Chugai Pharmaceutical Co.; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical Co.. 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; Financial Interests, Institutional, Invited Speaker: MSD, Daiichi-Sankyo, Ono Pharmaceutical, Astellas Pharma. H. Hara: Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb, Boehringer Ingelheim, Dainippon Sumitomo; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, MSD, Ono, Bayer, Chugai, Kyowa Hakko Kirin, Lilly, Merck Biopharma, Sanofi, Taiho, Takeda, Yakult; Financial Interests, Institutional, Invited Speaker: Amgen, Astellas, AstraZeneca, Bayel, BeiGene, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Janssen, Merck Biopharma, MSD, Ono, Taiho. T. Esaki: Financial Interests, Personal, Invited Speaker: Chugai, Taiho, EP force, MSD, Daiichi Sankyo, Eli Lilly, Ono; Financial Interests, Institutional, Research Grant: MSD, Novartis, Ono, Nihon Kayaku, IQVIA, Daiichi Sankyo, Chugai, Syneos Health Clinical, Pfyzer, Dainippon Sumitomo, Qluintiles, Eli Lilly, Parexel, Astellas, Astellas Amgen Biopharma; Financial Interests, Institutional, Funding: Taiho, Chugai, Nihon Kayaku. S. Kajiura: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo Company. T. Masuishi: Financial Interests, Personal, Invited Speaker: Takeda, Chugai, Merck Bio Pharma, Taiho, Bayer, Eli Lilly, Yakult Honsha, Sanofi, Daiichi Sankyo, Ono, Bristol myers squibb; Financial Interests, Institutional, Funding: Daiichi Sankyo, Ono, Novartis, Amgen, Syneos Healthe Clinical, Boehringer-Ingelheim, Pfizer, Cimic Shift Zero, Eli Lilly. E. Baba: Financial Interests, Personal, Speaker’s Bureau: Chugai, Taiho, Ono, BMS, MSD, Eli Lilly, Dai-ichi Sankyo, Yakult, Merck, Sanofi, Esai, Miyarisan, Novartis, Janssen; Financial Interests, Personal and Institutional, Research Grant: Chugai, Taiho, Eli Lilly; Financial Interests, Personal, Writing Engagements: Chugai, Dai-ichi Sankyo; Financial Interests, Personal, Advisory Board: Astellas, Eli Lilly, Dai-ichi Sankyo. K. Yoshimura: Financial Interests, Personal, Invited Speaker: Astra Zeneca, Chugai, Eli Lilly, MSD, Daiichi Sankyo, Kyowa Kirin, Ohara, Pfizer, Eizai. H. Kawakami: Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb Co. Ltd., Bayer Yakuhin Ltd, Eli Lilly Japan K.K., MSD K.K., Ono Pharmaceutical Co. Ltd, Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo 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.; Financial Interests, Personal, Other, Lecture: Glaxo Smith Kline 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., GlaxoSmithKline K.K., Sanofi K.K., Nippon Boehringer Ingelheim Co.,Ltd., Sysmex Corporation, Medical Reserch Support, Eli Lilly Japan K.K., Amgen Inc., Daiichi Sankyo Co., Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., SRL, Inc.. S. Hironaka: Financial Interests, Personal, Speaker’s Bureau: Ono pharmaceutical, Eli Lilly, Chugai phamaceutical, Merck biopharma, Taiho pharmaceutical, DaiichiSankyo, Bristol-Myers Squibb, MSD K.K., Yakult Honsha, AstraZeneca, Sanofi. K. Muro: Financial Interests, Institutional, Research Grant: Astellas, Amgen, Solasia Pharma, Sanofi, Daiichi Sankyo, Taiho, MSD, Parexel Internatinonal, Merck KGaA, Pfizer, Eisai, Ono; Financial Interests, Personal and Institutional, Advisory Board: Amgen, AstraZeneca, Ono, Chugai; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly, Daiichi Snakyo, Taiho, Ono, Brstol-Myers Squibb; Non-Financial Interests, Personal, Principal Investigator: Takeda. All other authors have declared no conflicts of interest.