HGCSG1901: A retrospective cohort study evaluating the safety and efficacy of S-1 and irinotecan plus bevacizumab in patients with metastatic colorectal cancer: Analysis of second-line treatment after anti-EGFR antibody

Background Although the selection of anti-EGFR antibody as first-line treatment for metastatic colorectal cancer (mCRC) patients is now decided based on primary tumor location and RAS mutational status, the best regimen as second-line treatment after anti-EGFR antibody has not been decided. Although the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines included a recommended regimen for irinotecan/S-1/BV (IRIS/Bev) as second-line treatment, no clinical trials had shown the efficacy and safety of IRIS/Bev after anti-EGFR antibody. Therefore, we performed this retrospective analysis in order to investigate the real-world efficacy and safety of IRIS/Bev as second-line treatment after anti-EGFR antibody in patients with mCRC (HGCSG1901). Methods We retrospectively analyzed the clinical data of 27 patients who received IRIS/Bev as second-line treatment after anti-EGFR antibody from August 2011 to March 2018 in 24 centers. IRIS/Bev regimen consisted of bevacizumab (5 mg/kg) given as an intravenous infusion on day 1 and day 15 of each 4-week cycle, followed by an intravenous infusion of irinotecan (100 mg/m2). S-1 (40-60 mg) was taken orally twice daily, from the night on day 1 to the morning on day 15, followed by a 14-day rest. In this study, CTCAE ver.4.01 and RECIST criteria ver.1.1 were used for analysis of adverse events (AEs) and response rate (RR)/disease control rate (DCR). The time to treatment failure (TTF), progression-free survival (PFS) and overall survival (OS) were estimated with Kaplan-Meier method. Results Patient characteristics were as follows; male/female 13/14, median age 57 (range 39-77), ECOG PS (0/1); 15/12, location of the primary site: right/left 7/20, KRAS exon 2 status: wild/mutant 26/1, prior anti-EGFR antibody: panitumumab/ cetuximab 17/10, UGT1A1 status; wild/single heterozygous/double heterozygous or homozygous/unknown 13/5/1/8. Relative dose intensity of irinotecan, S-1 and bevacizumab were 0.815 (range 0.274-1.000), 0.860 (range 0.510-1.021) and 0.895 (range 0.609-1.000), respectively. The common AEs (≥5%) of grade 3 or 4 were neutrophil count decreased (29.6%), white blood cell decreased (22.2%), hypertension (18.5%), diarrhea (14.8%), anemia (14.8%), anorexia (11.1%), and fatigue (11.1%). RR and DCR were 13.0% and 78.3%, respectively. Median TTF was 5.9 months (95%C.I. 4.9-6.8). The most common reasons for treatment discontinuation were disease progression (88.9%) and AEs (7.4%). Subsequent treatment was given to 24 (88.9%) of the 27 patients who discontinued IRIS/Bev. Median PFS and OS were 8.2 (95% confidence interval [C.I.] 5.3-11.1) and 14.7 months (95%C.I. 11.8-17.7), respectively. Conclusions In this retrospective analysis, IRIS/Bev in the real world clinical practice was an active and tolerated regimen as second-line treatment after anti-EGFR antibody in patients with mCRC. Clinical trial identification The study design and protocol were approved by the Institutional Review Board of Hokkaido University Hospital (approval number: 019-0210). Clinical trial information: UMIN000039077. Acknowledgement Thanks to the patients, their families, the investigators, study coordinators, and medical staff at 24 institutes. Legal entity responsible for the study The author. Funding This study was conducted by research funding of Nonprofit Organization (NPO), Hokkaido Gastrointestinal Cancer Study Group (HGCSG). Disclosure S. Yuki: Honoraria (self): Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Yakult Honsha Co. Ltd. M. Yagisawa: Honoraria (self): Taiho Parmaceutical Co., Ltd. M. Nakamura: Honoraria (self): Daiichi Sankyo, Chugai, Taiho. H. Nakatsumi: Honoraria (self): Ono Pharmaceutical, Bayer Yakuhin, Lilly Japan, Takeda Pharmaceutical, Chugai Pharma, Sanofi, Taiho Pharmaceutical. Y. Komatsu: Honoraria (self): TAIHO Phamaceutical Co., Ltd. Research grant / Funding (institution): TAIHO Phamaceutical Co., Ltd., CHUGAI Phamaceutical Co., Ltd. All other authors have declared no conflicts of interest.