Abstract 79P
Background
Regorafenib (REG) is one of the options for third- or later-line treatment for metastatic colorectal cancer (mCRC). Owing to the SUNLIGHT trial (Prager GW, et al. NEJM 2023), trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) has become a new standard third-line treatment for mCRC worldwide. The significance of using REG before and after FTD/TPI plus BEV has not been clarified.
Methods
We compared the clinical outcomes between REG-first (Group A) and FTD/TPI plus BEV-first (Group B) as third-line treatment using data from the OSERO study (UMIN000040586), a prospective, multicenter, non-randomized study in patients with mCRC. Stabilized inverse probability of treatment weights (IPTW) were calculated using a propensity score model with sex, age, ECOG PS, duration from date of first-line therapy, RAS status, tumor location, and number of metastatic sites as covariates considering the imbalance of patients’ background factors. The primary endpoint PFS2 was defined as time from initiation of treatment to second tumor progression or death from any cause.
Results
A total of 386 patients were classified into Group A (n = 154) and Group B (n = 232). Patients who received both REG and FTD/TPI plus BEV were 77 (50.0%) and 146 (62.9%) patients, respectively. After using IPTW, median overall survival (mOS) was 12.2 M in Group A and 10.6 M in Group B (hazard ratio [HR] 1.03; 95% confidence interval [CI] 0.81-1.30; p = 0.837) with the median follow-up time was 25.4 months. mPFS was 2.0 M and 3.8 M, respectively (HR 0.43; 95% CI 0.34-0.54; p < 0.0001). mPFS2 was 7.8 M in and 8.3 M, respectively (HR 0.94; 95% CI 0.70-1.27; p = 0.703). Grade ≥3 adverse events (AEs) with a frequency of ≥10% were hand-foot syndrome (14.9%), proteinuria (12.3%), and hypertension (11.0%) in Group A, and neutropenia (40.5%) and anemia (12.1%) in Group B.
Conclusions
REG before or after FTD/TPI plus BEV may contribute to prolong survival in mCRC. Therefore, it would be better to select the sequence of later-line treatment based on the difference of AE profiles.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Bayer.
Disclosure
T. Matsumoto: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb Company, Lilly Japan, Taiho Pharmaceutical, Daiichi Sankyo Company, Limited, Ono Pharmaceutical, Merck, Chugai Pharma, Daiichi Sankyo Company, Limited, Nippon Kayaku, Sanofi, Byer. T. Kawakami: Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Other, honoraria: Bristol Myers Squibb, Ono Pharmaceutical, Yakult Honsha, Daiichi Sankyo, Eli Lilly, Merck Biopharma, Taiho Pharmaceutical, AstraZeneca. T. Hamano: Financial Interests, Personal, Invited Speaker: Chugai pharmaceutical co. ltd.; Financial Interests, Institutional, Officer: P4 statistics co. ltd.; Financial Interests, Personal, Stocks/Shares: P4 statistics Co. Ltd. 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, MSD, Nippon Kayaku; Financial Interests, Institutional, Funding: Daiichi Sankyo, Ono, Novartis, Amgen, Syneos Healthe Clinical, Boehringer-Ingelheim, Pfizer, Cimic Shift Zero, Eli Lilly, MSD. 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. K. Harada: Financial Interests, Personal, Invited Speaker: MSD K.K., Eli Lilly Japan K.K., Bayer Yakuhin, Ltd., Nippon Kayaku Co.,Ltd., Ono Pharmaceutical Co., Ltd.), Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Bristol Myers Squibb, Servier, Daiichi Sankyo, Inc., AstraZeneca K.K. S. Boku: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bristol Myers Squibb, MSD Japan, Eisai Co., Ltd., Nippon Kayaku Co.,Ltd., Asahi Kasei Pharma Co.; Financial Interests, Institutional, Funding: Kyo Diagnostics Co., Ltd. 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. Yamamoto: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, CMIC holdings, Johokiko, AstraZeneca plc, Pfizer; Financial Interests, Personal, Other, Statistical consultation: Craif, Kanagawa Prefectural Hospital Organization; Financial Interests, Institutional, Other, unlimited grant: Taiho Pharmaceutical, Euro Doctor Concierge, LLC; Financial Interests, Institutional, Other, Unlimited grant: Takeda Pharmaceutical, Daiichi Sankyo, Kyowa Kirin, Chugai Pharmaceutical, Otsuka Pharmaceutical; Financial Interests, Personal, Advisory Board: Delta fly Farma, SRL Medisearch lnc., FUJIFILM Toyama Chemical Co., Ltd., Takeda Pharmaceutical Company Limited, TME Therapeutics Inc.; Financial Interests, Personal, Writing Engagement: Tokyo Shoseki Co., Ltd. S. Yuki: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Eli Lilly K.K., Takeda Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd, Bristol Myers Squibb Co., Ltd., Taiho Pharmaceutical Co., Ltd., MSD K.K., Ono Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Miyarisan Pharmaceutical Co., Ltd. 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. E. Oki: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Eli Lilly, Bristol Myers Squibb, MSD, Takeda Pham; Financial Interests, Institutional, Research Grant: Guardant Health. All other authors have declared no conflicts of interest.