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Efficacy of 2nd-line ramucirumab (RAM) plus FOLFIRI for RAS wild-type metastatic colorectal cancer (mCRC) by prior regimen: Subgroup analysis of the JACCRO CC-16
Background
There have been few studies which prospectively evaluated the efficacy and safety of RAM plus FOLFIRI after 1st-line anti-EGFR antibody-containing therapy in RAS wild-type mCRC. We therefore conducted a multicenter phase 2 trial, JACCRO CC-16, and reported 6month-PFS rate of 58.2 % and median PFS of 7.0 months.
Methods
The JACCRO CC-16 was a single arm, phase 2 trial to evaluate the efficacy and safety of RAM (8 mg/kg) plus FOLFIRI (irinotecan 150 mg/m2, bolus 5-FU 400 mg/m2, infusional 5-FU 2400 mg/m2) in mCRC patients with RAS wild-type tumors and ECOG PS 0 or 1, after 1st-line oxaliplatin-based doublet (Ox-doublet) or triplet plus anti-EGFR antibody. Primary endpoint was 6month-PFS rate. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), early tumor shrinkage (ETS), and overall survival. The subgroup post-hoc analysis was performed to investigate the differences in clinical outcomes of RAM plus FOLFIRI according to previous 1st-line regimen, doublet or triplet.
Results
A total of 92 patients were enrolled between October 2018 and 2020 December. Ninety-one patients were analyzed as the full analysis set. In prior 1st-line treatment, 19 (21%) patients were treated with modified-FOLFOXIRI plus cetuximab, and 72 (79%) patients were treated with doublet plus anti-EGFR antibody. The doublet group included 3 patients who failed to achieve an ETS during 1st-line treatment. The 6months-PFS rate (95% CI) was 57.9 % (33.2 to 76.3) in the triplet group and 58.3 % (46.1 to 68.7) in the doublet group. The PFS was significantly longer in the doublet group (median PFS, 7.4 months, 95% CI 5.7 to 9.0) compared to the triplet group (median PFS, 6.4 months, 95% CI 3.8 to 7.35) (p = 0.036, log-rank test). The ORR and DCR were 5.6 % and 94.4 % in the triplet group and 12.1 % and 84.8 % in the doublet group, with no significant difference between 2 groups (p = 0.42 and p = 0.28, respectively).
Conclusions
This study demonstrated a favorable efficacy of FOLFIRI plus RAM treatment in RAS wild-type mCRC patients treated with 1st-line anti-EGFR antibody-containing therapy. It may also achieve a certain effect in cases previously treated with triplet-based regimen.
Clinical trial identification
jRCTs061180002.
Legal entity responsible for the study
The authors.
Funding
This study is funded by Eli Lilly Japan K.K.
Disclosures
A. Tsuji: Speaker Bureau / Expert testimony: Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd. , Eli Lilly Japan Co., ; Research grant / Funding (institution): Taiho Pharmaceutical Co., Ltd. , Sanofi Corporation , Ono Pharmaceutical Co.,. H. Satake: Honoraria (self): Ono pharmaceutical co., ltd., Daiichi Sankyo Co., Ltd., Eli Lilly Japan Co., Ltd., Merck Bio Pharma Co., Ltd., MSD Co., Ltd., Bayer Co., Ltd., Bristol-Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Sanofi Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Co., Ltd. and Yakult Honsha Co., Ltd.; Research grant / Funding (institution): Ono pharmaceutical co., ltd., Daiichi Sankyo, Takeda Pharmaceutical Co., Ltd., Sanofi, Taiho Pharmaceutical Co., Ltd. H. Yasui: Honoraria (self): Daiichi Sankyo, Ono Pharmaceutical, Taiho Pharmaceutical, Chugai Pharma, Bristol-Myers Squibb Japan, TERUMO, Eli Lilly Japan, Merk Biopharma, Yakult Honsha, Bayer Yakuhin, Takeda Pharmaceutical; Research grant / Funding (self): MSD, Ono Pharmaceutical, Daiichi Sankyo, Astellas Pharma. M. Nakamura: Honoraria (self): Bayer Yakuhin, Ltd., Bristol-Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan Co., Ltd., Merck Bio Pharma Co., Ltd., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Yakult Honsha Co., Ltd. Y. Sunakawa: Honoraria (self): Bristol-Myers Squibb, Chugai Pharm, Eli Lilly Japan; Advisory / Consultancy: Daiichi-Sankyo, Bristol-Myers Squibb, Guardant Health; Research grant / Funding (self): Chugai Pharm, Takeda, Taiho Pharm. M. Kotaka: Honoraria (self): Chugai pharmaceutical, Lilly. T. Masuishi: Honoraria (self): Taiho, Lilly, Chugai, Yakult Honsha. W. Ichikawa: Honoraria (self): Chugai Pharma, Merck Biopharma; Research grant / Funding (institution): Taiho Pharma, Chugai Pharma, Takeda Pharma. All other authors have declared no conflicts of interest.
