Regorafenib Versus Trifluridine/Tipiracil for Refractory Metastatic Colorectal Cancer: A Retrospective Comparison.
Regorafenib and trifluridine/tipiracil (TAS-102) both prolong survival for patients with refractory metastatic colorectal cancer. However, it is unclear which drug should be administered first.



We retrospectively evaluated the data from patients who had received regorafenib or TAS-102 at 2 institutions from May 2013 to March 2015. The inclusion criteria were disease refractory or intolerant to fluoropyrimidines, oxaliplatin, irinotecan, anti-vascular endothelial growth factor antibodies, and anti-epidermal growth factor receptor (EGFR) antibodies (if KRAS exon 2 wild-type), and no previous treatment with regorafenib or TAS-102.



A total of 146 and 54 patients received regorafenib and TAS-102, respectively. The baseline characteristics were similar between the 2 groups, except for a history of irinotecan and anti-EGFR therapy and high alkaline phosphatase levels. The median progression-free survival and overall survival were 2.1 months and 6.7 months, respectively, with regorafenib and 2.1 months and 6.5 months, respectively, with TAS-102 (progression-free survival hazard ratio 1.20, P = .27; overall survival hazard ratio, 1.01, P = .97). The analysis of overall survival for patients after the approval of TAS-102 in Japan was similar to the overall survival for the entire population. The frequency of hand-foot syndrome and increased aspartate aminotransferase, alanine aminotransferase, and bilirubin levels was higher and the frequency of neutropenia, leukopenia, anemia, nausea, and febrile neutropenia was lower with regorafenib than with TAS-102. No remarkable differences were found in the efficacy and safety of TAS-102 between patients with and without previous regorafenib and vice versa.



Regorafenib and TAS-102 had similar efficacy but resulted in different toxicities, which could guide the agent choice.
Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
Toshiki
T
Masuishi
Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan. Electronic address: h.taniguchi@aichi-cc.jp.
Hiroya
H
Taniguchi
Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
Satoshi
S
Hamauchi
Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
Azusa
A
Komori
Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
Yosuke
Y
Kito
Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
Yukiya
Y
Narita
Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
Takahiro
T
Tsushima
Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan.
Makoto
M
Ishihara
Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
Akiko
A
Todaka
Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan.
Tsutomu
T
Tanaka
Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
Tomoya
T
Yokota
Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
Shigenori
S
Kadowaki
Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
Nozomu
N
Machida
Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
Takashi
T
Ura
Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
Akira
A
Fukutomi
Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
Masashi
M
Ando
Division of Clinical Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
Yusuke
Y
Onozawa
Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan.
Masahiro
M
Tajika
Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
Hirofumi
H
Yasui
Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
Kei
K
Muro
Clinical Research Center, Shizuoka Cancer Center, Shizuoka, Japan.
Keita
K
Mori
Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
Kentaro
K
Yamazaki
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D011759:Pyrrolidines; D012189:Retrospective Studies; D015996:Survival Rate; D013941:Thymine; D016896:Treatment Outcome; D014271:Trifluridine / Q000008:administration & dosage* / Q000009:adverse effects; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
D000970:Antineoplastic Agents; D004338:Drug Combinations; D010671:Phenylurea Compounds; D011725:Pyridines; D011759:Pyrrolidines; C000613803:trifluridine tipiracil drug combination; C559147:regorafenib; D014498:Uracil; D013941:Thymine; D014271:Trifluridine
Adverse event; Chemotherapy; Clinical practice; Efficacy; Subsequent treatment