Clinical Impact of Primary Tumor Location in Metastatic Colorectal Cancer Patients Under Later-Line Regorafenib or Trifluridine/Tipiracil Treatment

Hiromichi Nakajima; Shota Fukuoka; Toshiki Masuishi; Atsuo Takashima; Yosuke Kumekawa; Takeshi Kajiwara; Kentaro Yamazaki; Yuji Negoro; Masato Komoda; Akitaka Makiyama; Tadamichi Denda; Yukimasa Hatachi; Takeshi Suto; Naotoshi Sugimoto; Masanobu Enomoto; Toshiaki Ishikawa; Tomomi Kashiwada; Koji Ando; Satoshi Yuki; Hiroyuki Okuyama; Hitoshi Kusaba; Daisuke Sakai; Koichi Okamoto; Takao Tamura; Kimihiro Yamashita; Masahiko Gosho; Toshikazu Moriwaki

doi:10.3389/fonc.2021.688709

Clinical Impact of Primary Tumor Location in Metastatic Colorectal Cancer Patients Under Later-Line Regorafenib or Trifluridine/Tipiracil Treatment

Front Oncol. 2021 Jun 15:11:688709. doi: 10.3389/fonc.2021.688709. eCollection 2021.

Authors

Hiromichi Nakajima¹, Shota Fukuoka², Toshiki Masuishi³, Atsuo Takashima⁴, Yosuke Kumekawa⁵, Takeshi Kajiwara⁶, Kentaro Yamazaki⁷, Yuji Negoro⁸, Masato Komoda⁹, Akitaka Makiyama^{10

11}, Tadamichi Denda¹², Yukimasa Hatachi¹³, Takeshi Suto¹⁴, Naotoshi Sugimoto¹⁵, Masanobu Enomoto¹⁶, Toshiaki Ishikawa¹⁷, Tomomi Kashiwada¹⁸, Koji Ando¹⁹, Satoshi Yuki²⁰, Hiroyuki Okuyama²¹, Hitoshi Kusaba²², Daisuke Sakai²², Koichi Okamoto²³, Takao Tamura²⁴, Kimihiro Yamashita²⁵, Masahiko Gosho²⁶, Toshikazu Moriwaki²⁷

Affiliations

¹ Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan.
² Division of Cancer Immunology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan.
³ Department of Clinical Oncology, Aichi Cancer Center Hospital, Aichi, Japan.
⁴ Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
⁵ Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan.
⁶ Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Ehime, Japan.
⁷ Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
⁸ Clinical Oncology Division, Kochi Health Sciences Center, Kochi, Japan.
⁹ Department of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
¹⁰ Department of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital, Fukuoka, Japan.
¹¹ Cancer Center, Gifu University Hospital, Gifu, Japan.
¹² Division of Gastroenterology, Chiba Cancer Center, Chiba, Japan.
¹³ Department of Clinical Oncology, Kansai Rosai Hospital, Hyogo, Japan.
¹⁴ Department of Gastroenterological Surgery, Yamagata Prefectural Central Hospital, Yamagata, Japan.
¹⁵ Department of Medical Oncology, Osaka International Cancer Institute, Osaka, Japan.
¹⁶ Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan.
¹⁷ Department of Specialized Surgeries, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, Tokyo, Japan.
¹⁸ Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.
¹⁹ Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
²⁰ Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Hokkaido, Japan.
²¹ Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
²² Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
²³ Department of Surgery, National Defense Medical College, Saitama, Japan.
²⁴ Department of Medical Oncology, Faculty of Medicine, Kindai University, Osaka, Japan.
²⁵ Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Hyogo, Japan.
²⁶ Department of Biostatistics, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
²⁷ Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.

Abstract

Background: Primary tumor location (PTL) is an important prognostic and predictive factor in the first-line treatment of metastatic colorectal cancer (mCRC). Although regorafenib (REG) and trifluridine/tipiracil (FTD/TPI) have been introduced recently, the clinical impact of PTL in these treatments is not well understood.

Materials and methods: We retrospectively evaluated patients with mCRC who were registered in a multicenter observational study (the REGOTAS study). The main inclusion criteria were Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2, refractory or intolerant to fluoropyrimidines, oxaliplatin, irinotecan, angiogenesis inhibitors, anti-epidermal growth factor receptor therapy (if RAS wild-type), and no prior use of REG and FTD/TPI. The impact of PTL on overall survival (OS) was evaluated using Cox proportional hazard models based on baseline characteristics.

Results: A total of 550 patients (223 patients in the REG group and 327 patients in the FTD/TPI group) were included in this study, with 122 patients with right-sided tumors and 428 patients with left-sided tumors. Although the right-sided patients had significantly shorter OS compared with the left-sided patients by univariate analysis (p = 0.041), a multivariate analysis revealed that PTL was not an independent prognostic factor (hazard ratio, 0.95; p = 0.64). In a subgroup analysis, the OS was comparable between the REG and FTD/TPI groups regardless of PTL (p for interactions = 0.60).

Conclusions: In the present study, PTL is not a prognostic and predictive factor in patients with mCRC under later-line REG or FTD/TPI therapy.

Keywords: biomarker; colorectal cancer; primary tumor location; regorafenib; trifluridine/tipiracil.

Copyright © 2021 Nakajima, Fukuoka, Masuishi, Takashima, Kumekawa, Kajiwara, Yamazaki, Negoro, Komoda, Makiyama, Denda, Hatachi, Suto, Sugimoto, Enomoto, Ishikawa, Kashiwada, Ando, Yuki, Okuyama, Kusaba, Sakai, Okamoto, Tamura, Yamashita, Gosho and Moriwaki.