Abstract 442TiP
Background
Survival outcome of patients (pts) who underwent a curative resection for BRAF V600E-mutatnt colorectal oligometastases (CROM) is poor. We have previously reported that survival outcome of pts with surgically resectable BRAF V600E-mutatnt colorectal liver metastases (CRLM) was as poor as unresectable cases (OS, 14.4 vs. 17.2 months, P=0.65). Therefore, surgically resectable BRAF V600E-mutatnt CROM are mostly oncologically unresectable, and development of new perioperative treatment is warranted. On the other hand, a combination of encorafenib (ENCO), binimetinib (BINI) plus cetuximab (CETUX) was reported to prolong OS compared with FOLFIRI (Irinotecan) + CETUX in pts with previously treated unresectable BRAF V600E-mutatnt colorectal cancer (BEACON CRC trial).
Trial design
This is a multicenter, open-label, prospective phase II study to evaluate the efficacy and safety of perioperative use of the triplet therapy in pts with previously untreated surgically resectable BRAF V600E-mutatnt CROM (jRCT2031220025). The triplet therapy (ENCO: 300 mg daily, BINI: 45 mg twice daily, CETUX: 400 mg/m2 of body-surface area as an initial dose, then 250 mg/m2 weekly, 28 days in a cycle) is offered for 3 cycles each before and after the curative resection. The primary end point is 1-year progression-free survival (PFS) rate and the secondary end points are PFS, DFS, OS, pathological response, R0 resection rate and so on. As the 1-year DFS in pts with BRAF V600E-mutatnt CRLM was 24% in Japan and the hazard ratio of the triplet therapy for PFS in the BEACON CRC trial was 0.42, 25% and 50% were set as the threshold and expected value respectively for the 1-year PFS rate in this study. Planed patient accrual is set as 32 pts with the one-sided significance level at 2.5% and the statistical power at 80%. The study started in April 2022. The results will be compared with a real-world data of pts who undergo surgery for BRAF V600E-mutatnt CROM that is retrieved from the regulatory-conformed national registry (Circulate-Japan GALAXY study).
Clinical trial identification
jRCT2031220025.
Editorial acknowledgement
Legal entity responsible for the study
National Cancer Center Hospital East, Japan.
Funding
Japan Agency for Medical Research and Development.
Disclosure
H. Bando: Financial Interests, Institutional, Research Grant: Ono pharmaceutical; Other, Other, Lecture fee: Ono pharmaceutical, Taiho pharmaceutical, Eli Lilly Japan. 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. 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. T. Kato: Financial Interests, Personal, Invited Speaker: CHUGAI PHARMACEUTICAL CO., LTD, Eli Lilly and Company, ONO Pharmaceutical Co, Takeda Pharmaceutical Company Limited, ASAHIKASEI; Financial Interests, Institutional, Research Grant: CHUGAI PHARMACEUTICAL CO. Y. Kagawa: Financial Interests, Personal, Invited Speaker: Bayer, Chugai, Yakult, Sanofi, Eli Lilly, Taiho, Takeda, Merck, Ono. T. Yoshino: Financial Interests, Personal, Invited Speaker: Chugai, Merck Biopharma, Bayer, Ono, MSD; Financial Interests, Institutional, Invited Speaker: Ono, Sanofi, Daiichi Sankyo, Chugai, Pfizer; Financial Interests, Institutional, Research Grant: Taiho, MSD, Ono, Amgen, Genomedia, Sysmex, Daiichi Sankyo, Chugai, Boehringer Ingelheim. All other authors have declared no conflicts of interest.