P-81 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

Abstract

The FIRIS trial, which is a phase III trial, showed non-inferiority of S-1 and irinotecan (IRIS) to FOLFIRI as second-line treatment for metastatic colorectal cancer (mCRC) patients. In addition, the ML18147 study showed the survival benefit of bevacizumab (Bev) combination treatment after progression to first-line treatment with Bev. Based on these results, IRIS/Bev is recommended as second-line treatment for mCRC patients in the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines. However, there are few studies exploring the efficacy and safety of IRIS/Bev for the second-line setting in real-world practice. Therefore, we performed this retrospective analysis in order to investigate the real-world efficacy and safety of IRIS/Bev as second-line treatment in patients with mCRC (HGCSG1901). We retrospectively analyzed the clinical data of 284 patients who received IRIS/Bev as second-line treatment from August 2011 to March 2018 in 24 centers. IRIS/Bev regimen consisted of bevacizumab (5 mg/kg) given as an intravenous infusion, followed by an intravenous infusion of irinotecan (100 mg/m2) on day 1 and day 15 of each 4-week cycle. 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 the Kaplan-Meier method. Patient characteristics were as follows; male/female 159/125, median age 65 (range 30-82), ECOG PS (0/1/2) 188/91/5, location of the primary site right/left 100/184, KRAS status wild/mutant/unknown 130/145/9, UGT1A1 status wild/single heterozygous/double heterozygous or homozygous/unknown 99/65/5/9/106. Median relative dose intensity of irinotecan, S-1 and bevacizumab were 0.752 (range 0.055-1.120), 0.799 (range 0.010-1.120), and 0.835 (range 0.021-1.120), respectively. The common AEs (≥5%) of grade 3 or 4 were decreased neutrophil count (23.5%), decreased white blood cells (16.6%), diarrhea (16.5%), anemia (12.0%), anorexia (9.5%), hypertension (9.2%), fatigue (6.0%), and febrile neutropenia (5.3%). RR and DCR were 14.7% and 76.6%, respectively. Median TTF was 5.9 months (95%C.I. 5.0-6.7). The common reason for treatment discontinuation were disease progression (72.4%) and AEs (16.0%). Subsequent treatment was given to 209 (76.0%) of the 275 patients who discontinued IRIS/Bev. Median PFS and OS were 7.2 (95%C.I. 6.3-8.0) and 16.3 months (95%C.I. 14.4-18.3), respectively. In this retrospective analysis, IRIS/Bev in real-world clinical practice showed efficacy comparable to other standard second-line treatments for mCRC. In this study, the incidence of diarrhea (≥ Grade 3) was 16.5%, which was lower than the incidence of diarrhea (≥ Grade 3) with IRIS (20.5%) in the FIRIS study. Diarrhea of IRIS/Bev as second-line treatment for mCRC was manageable with appropriate dose reduction and interruption.