615P - The impacts of starting regorafenib dose on treatment outcomes in metastatic colorectal cancer

Background

Based on the results of the ReDOS study, starting a reduced dose of regorafenib (REG) is considered a treatment option for patients with metastatic colorectal cancer (mCRC). However, the effect of starting REG at a reduced dose on treatment outcomes in a real-world setting has not been fully investigated.

Methods

Clinical data ofpatients who received REG for mCRC between May 2013 and December 2020 were retrospectively collected from four institutions in Japan. These patients were divided into two groups: those who received a standard starting dose of REG (Group S) and those who received a reduced starting dose of REG (Group R). Treatment outcomes were compared between the two groups using Cox proportional hazards models based on propensity score adjustment for baseline characteristics.

Results

A total of 573 patients were enrolled (299 in Group S and 274 in Group R). After propensity score matching, 151 patients each in Group S and R were analyzed. The median overall survival was 6.4 months [95% C.I. 5.5-7.4] in Group S, and 6.1 month [95% C.I. 5.1-7.1] in Group R, respectively (HR 1.018, p=0.882). The median progression free survival was 2.1 months [95% C.I. 1.8-2.4] in Group S and 2.1 months [95%C.I. 1.8-2.3] in Group R, respectively (HR 1.077, p=0.522). The median time to the first dose reduction was 33.0 days [95% C.I. 29.1-36.9] in Group S and 74.0 days [95% C.I. 30.6-117.4] in Group R (HR 0.613, p=0.002). The median time to the first dose interruption was 14.0 days [95% C.I. 13.3-14.7] in Group S and 16.0 days [95% C.I. 11.9-20.1] in Group R (HR 0.757, p=0.033). Both any grades and ≥grade 3 proteinuria were significantly less frequent in Group R than in Group S (any grades: 68.7% vs 53.8%, p=0.027, ≥grade 3: 11.3% vs. 3.8%, p=0.045). The median time to onset of any grades and ≥grade 3 proteinuria was significantly longer in Group R (any grades: HR 0.711, p=0.042, ≥grade 3: HR 0.338, p=0.045). No significant difference was observed in the frequency of hand foot skin reaction and hypertension between the two groups.

Conclusions

Our results suggest that starting a reduced dose of REG contributes to a reduction in the frequency and delay in the onset of proteinuria without any impact on efficacy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

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., Yakult Honsha Co., Ltd., Merck Biopharma Co., Ltd., Sanofi K.K., Daiichi Sankyo Co., Ltd.. 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. T. Kawakami: Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Other, honoraria: Bristol Myers Squibb, Ono Pharmaceutical, Yakult Honsha, Daiichi Sankyo. S. Kadowaki: Financial Interests, Personal, Invited Speaker: Taiho, MSD, Ono, Daiichi Sankyo, Bristol Myers Squibb, Bayer, Merck, Eisai, Otsuka; Financial Interests, Institutional, Funding: Eli Lilly, MSD, Ono, Daiichi Sankyo, Chugai, Nobelpharma, Yansen. H. Taniguchi: Financial Interests, Personal, Invited Speaker: Ono, Takeda, Eli Lilly, Chugai, Taiho, Merck Biopharma; Financial Interests, Institutional, Coordinating PI: Takeda, Daiichi Sankyo; Financial Interests, Institutional, Local PI: Ono. K. Muro: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Ono, Chugai; Financial Interests, Personal, Invited Speaker: Eli Lilly, Ono, Daiichi Sankyo, Taiho, Bristol Myers Squibb, Takeda, Chugai, AstraZeneca, Amgen; Financial Interests, Institutional, Research Grant, Including local PI as role: Astellas, Amgen, Sanofi, Daiichi Sankyo, Taiho, MSD, Pfizer, Merck Biopharma, Eisai, Ono, Novartis; Non-Financial Interests, , Principal Investigator: Takeda. Y. Kawamoto: Financial Interests, Personal, Invited Speaker: Eli Lilly Japan K.K., Yakult Honsha Co. Ltd., Merck KGaA, Incyte Biosciences Japan, Taiho Pharmaceutical Co. Ltd., Ono Pharmaceutical Co. Ltd; Financial Interests, Institutional, Funding: Takeda Pharmaceutical Co. Ltd. Y. Komatsu: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd., Daiichi Sankyo, Taiho, Chugai, Lilly, Merck, MSD, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical Co., Ltd., Taiho, Chugai, Sanofi, Nipro, Daiichi Sankyo, Bristol Myers Squibb; Non-Financial Interests, Member: JSCO, JSMO, ASCO. E. Oki: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical Co. Ltd., Ono Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Bayer, Eli Lilly, Bristol Myers Squibb, MSD; Financial Interests, Personal and Institutional, Research Grant: Guardant Health. 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. 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. All other authors have declared no conflicts of interest.