TY - JOUR
T1 - Phase II trial of aflibercept with FOLFIRI as a second-line treatment for Japanese patients with metastatic colorectal cancer
AU - Denda, Tadamichi
AU - Sakai, Daisuke
AU - Hamaguchi, Tetsuya
AU - Sugimoto, Naotoshi
AU - Ura, Takashi
AU - Yamazaki, Kentaro
AU - Fujii, Hirofumi
AU - Kajiwara, Takeshi
AU - Nakajima, Takako Eguchi
AU - Takahashi, Shin
AU - Otsu, Satoshi
AU - Komatsu, Yoshito
AU - Nagashima, Fumio
AU - Moriwaki, Toshikazu
AU - Esaki, Taito
AU - Sato, Takeo
AU - Itabashi, Michio
AU - Oki, Eiji
AU - Sasaki, Toru
AU - Sunaga, Yoshinori
AU - Ziti-Ljajic, Samira
AU - Brillac, Claire
AU - Yoshino, Takayuki
N1 - Funding Information:
The authors thank all patient participants. This study was funded by Sanofi and medically supervised by Ichinosuke Hyodo (Tsukuba University) and Hiromichi Suzuki (Musashino Tokushukai Hospital). Independent monitoring of safety and efficacy was provided by the Efficacy and Safety Evaluation Committee (Hiroyuki Uetake, Tokyo Medical and Dental University; Yoshihiko Tomita, Niigata University; and Ichiei Narita, Niigata University). Writing assistance
Funding Information:
TH received honoraria from Taiho, Chugai, Takeda, Yakult and Merck Serono, a consulting fee from NanoCarrier, and research funding from MSD, Ono, Sanofi, Daiichi Sankyo, Sumitomo Dainippon Pharma, Taiho, Teijin and NanoCarrier. NS received honoraria from Chugai and Eli Lilly, and research funding from Chugai, Eli Lilly, Dainippon Sumitomo, Taiho, MSD, Ono, Dai-ichi Sankyo and Sanofi. TU received honoraria from Merck Serono, Taiho, Chugai and Takeda, and research funding from Sanofi. KY received honoraria from Chugai, Takeda, Yakult, Daiichi-sankyo, Merck Serono, Bristol, Bayer, Eli Lilly and Taiho, and research funding from BMS and Sanofi. HF received research funding from Sanofi. ST received honoraria from Asahikasei, and research funding from Merck Serono, Ono and Sanofi. YK received honoraria from BMS and Sanofi, and research funding from Eli-Lilly, BMS and Sanofi. TE received honoraria from Eli Lilly, and research funding from Boehringer, Daiichi-Sankyo, Dainippon Sumitomo, Eli Lilly, Merck Serono, MSD, Novartis, Ono and Taiho, and a scholarship from Ono. EO received honoraria from Bayer, Chugai, Eli Lilly, Merck Serono, Taiho, Takeda and Yakult. TY received honoraria from Chugai, Eli Lilly, Merck Serono, Sanofi and Taiho, and research funding from Boehringer Ingelheim, Chugai, Dainippon Sumitomo, GlaxoSmithKline, MSD, Novartis and Sanofi. The affiliated medical institutions of physician authors received study funding from Sanofi. TS, YS, SZL and CB are employees of Sanofi. Funding for this research was provided by Sanofi. Because Sanofi is the company that initiated the
PY - 2019/3
Y1 - 2019/3
N2 - Aflibercept targets vascular endothelial growth factor. The present study involved assessing the efficacy, safety and pharmacokinetics of aflibercept plus 5-fluorouracil/levofolinate/irinotecan (FOLFIRI) as a second-line treatment for metastatic colorectal cancer (mCRC) in Japanese patients. Aflibercept (4 mg/kg) plus FOLFIRI was administered every 2 weeks in 62 patients with mCRC until disease progression, unacceptable toxicity or patient withdrawal. Tumors were imaged every 6 weeks. The primary endpoint was objective response rate (ORR); secondary endpoints were progression-free survival, overall survival, safety, and pharmacokinetics of aflibercept, irinotecan and 5-fluorouracil. A total of 60 patients were evaluated for ORR; 50 had received prior bevacizumab. The ORR was 8.3% (95% confidence interval [CI]: 1.3%-15.3%), and the disease control rate (DCR) was 80.0% (69.9%-90.1%). The median progression-free survival was 5.42 months (4.14-6.70 months) and the median overall survival was 15.59 months (11.20-19.81 months). No treatment-related deaths were observed, and no significant drug-drug interactions were found. The most common treatment-emergent adverse events were neutropenia and decreased appetite. Free aflibercept had a mean maximum concentration (coefficient of variation) of 73.2 μg/mL (15%), clearance of 0.805 L/d (22%) and volume of distribution of 6.2 L (18%); aflibercept bound with vascular endothelial growth factor had a clearance of 0.162 L/d (9%) (N = 62). Aflibercept did not significantly affect the pharmacokinetics of irinotecan or 5-fluorouracil: The clearance was 11.1 L/h/m2 (28%) for irinotecan and, at steady state, 72.6 L/h/m2 (56%) for 5-fluorouracil (N = 10). Adding aflibercept to FOLFIRI was shown to be beneficial and well-tolerated in Japanese patients with mCRC. ClinicalTrials.gov Identifier: NCT01882868.
AB - Aflibercept targets vascular endothelial growth factor. The present study involved assessing the efficacy, safety and pharmacokinetics of aflibercept plus 5-fluorouracil/levofolinate/irinotecan (FOLFIRI) as a second-line treatment for metastatic colorectal cancer (mCRC) in Japanese patients. Aflibercept (4 mg/kg) plus FOLFIRI was administered every 2 weeks in 62 patients with mCRC until disease progression, unacceptable toxicity or patient withdrawal. Tumors were imaged every 6 weeks. The primary endpoint was objective response rate (ORR); secondary endpoints were progression-free survival, overall survival, safety, and pharmacokinetics of aflibercept, irinotecan and 5-fluorouracil. A total of 60 patients were evaluated for ORR; 50 had received prior bevacizumab. The ORR was 8.3% (95% confidence interval [CI]: 1.3%-15.3%), and the disease control rate (DCR) was 80.0% (69.9%-90.1%). The median progression-free survival was 5.42 months (4.14-6.70 months) and the median overall survival was 15.59 months (11.20-19.81 months). No treatment-related deaths were observed, and no significant drug-drug interactions were found. The most common treatment-emergent adverse events were neutropenia and decreased appetite. Free aflibercept had a mean maximum concentration (coefficient of variation) of 73.2 μg/mL (15%), clearance of 0.805 L/d (22%) and volume of distribution of 6.2 L (18%); aflibercept bound with vascular endothelial growth factor had a clearance of 0.162 L/d (9%) (N = 62). Aflibercept did not significantly affect the pharmacokinetics of irinotecan or 5-fluorouracil: The clearance was 11.1 L/h/m2 (28%) for irinotecan and, at steady state, 72.6 L/h/m2 (56%) for 5-fluorouracil (N = 10). Adding aflibercept to FOLFIRI was shown to be beneficial and well-tolerated in Japanese patients with mCRC. ClinicalTrials.gov Identifier: NCT01882868.
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U2 - 10.1111/cas.13943
DO - 10.1111/cas.13943
M3 - Article
C2 - 30657223
AN - SCOPUS:85062383382
VL - 110
SP - 1032
EP - 1043
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 3
ER -