Abstract 38P
Background
A randomized phase II DEEPER trial (JACCRO CC-13)[NCT02515734] has demonstrated a significantly better depth of response (DpR) in m-FOLFOXIRI plus cetuximab (cet) compared to bevacizumab (bev) as initial therapy in RAS wild-type (wt) mCRC patients (pts). In left-sided and RAS/BRAF wt pts, progression-free survival (PFS) was better in the cet arm (median; 14.5 vs. 11.9 months, HR 0.71) [ESMO 2023]. Here, we report the efficacy of m-FOLFOXIRI plus cet in mCRC pts with right-sided or BRAF mutant tumors.
Methods
The primary endpoint was DpR in per protocol set (PPS) consisted of pts evaluable for the DpR. Secondary endpoints included PFS, overall survival, overall response rate (ORR), early tumor shrinkage rate, resection rate, and toxicity. The sidedness was used as a stratification factor for randomization. BRAF status was identified in 73% pts of PPS by collection from medical record or analysis of BRAF gene in the biomarker study. All statistical tests are two-sided, and P values ≤ 0.05 are deemed significant.
Results
In 321 pts of PPS, 52 and 22 pts were right-sided and BRAF mutant tumors, respectively. In right-sided pts, median DpR was 50.0% vs. 41.2% in the cet vs. bev arm (P=0.47). It was 45.7% vs. 38.3% (P=0.77) in BRAF mutant pts. A sub-group analysis of median DpR by sidedness/BRAF status showed 53.3% vs. 58.9% for right/wt, 46.7% vs. 28.2% for right/mutant, 20.3% vs. 56.9% for left/mutant. ORR and R0 resection rate were not different between 2 arms in right-sided or BRAF mutant pts. In right-sided pts, median PFS was 9.0 months vs. 12.8 months (HR 1.54, P=0.14) in the cet vs. bev arm, respectively. In right-sided and BRAF wt pts, PFS in the bev arm was better (median, 14.7 vs. 9.7 months). In BRAF mutant pts, median PFS was 4.6 months vs. 8.4 months (HR 4.65, P=0.0016) in the cet vs. bev arm, respectively; moreover, PFS was worse in the cet arm for both left and right primary sites.
Conclusions
In right-sided or BRAF mutant mCRC pts, m-FOLFOXIRI plus cet had shorter PFS compared to m-FOLFOXIRI plus bev although DpR was not worse in the cet arm. Also, triplet plus cet was not clinically beneficial for left-sided mCRC pts with BRAF mutant tumors.
Clinical trial identification
NCT02515734.
Legal entity responsible for the study
M. Fujii.
Funding
Merck Biopharma Co., Ltd.
Disclosure
Y. Sunakawa: Financial Interests, Personal, Invited Speaker: Eli Lilly Japan, Bristol-Byers Squibb, Chugai Pharmaceutical, Takeda, Taiho Pharmaceutical, Merck Biopharma, Daiichi Sankyo, Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Merck Biopharma; Financial Interests, Personal and Institutional, Research Grant: Chugai Pharmaceutical, Taiho Pharmaceutical, Takeda, Otsuka Pharm, Parexel International Inc., IQVIA, Ono Pharmaceutical, CMIC Shift Zero K.K., PRA health sciences, Inc., Amgen; Non-Financial Interests, Project Lead: Japan Clinical Cancer Research Organization. M. Shiozawa: Financial Interests, Personal, Invited Speaker: Lilly Japan, Merck Serono, Taiho Pharmaceutical, Yakult Honsha, Takeda, Ono Pharmaceutical, Johnson & Johnson, Kaken. H. Yasui: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Chugai Pharma, Bristol Myers Squibb, Daiichi Sankyo, Terumo, Eli Lilly Japan, Merck Biopharma, Yakult Honsha, Bayer Yakuhin; Financial Interests, Institutional, Invited Speaker: MSD, Daiichi Sankyo, Ono Pharmaceutical, Astellas Pharma, Amgen. H. Ohori: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical Co., Ltd., Daiichi Sankyo Company Limited., Nippon Kayaku, Co., Ltd., Chugai Pharmaceutical Co., Ltd., MSD K.K., Bristol Myers Squibb Company, Takeda Pharmaceutical Company Limited., Eli Lilly Japan K.K., Yakult Honsha Co., Ltd. W. Ichikawa: Financial Interests, Personal, Invited Speaker: Merck BioPharma, Bristol Myers Squibb, Chugai Pharmaceutical, Yakult Honsha, AstraZeneca, Daiichi Sankyo, Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo, Shionogi, Takeda Pharmaceutical. A. Tsuji: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Eli Lilly Japan Co., Ltd., MSD Corporation, Daiichi Sankyo Co., Ltd., Bristol Myers Squibb Corporation, Merck Biopharma Co., Ltd., Chugai Pharmaceutical Co., Ltd.; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.