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Third- or Later-line Therapy for Metastatic Colorectal Cancer: Reviewing Best Practice.

  • Bekaii-Saab, Tanios1
  • Kim, Richard2
  • Kim, Tae Won3
  • O'Connor, Juan Manuel4
  • Strickler, John H5
  • Malka, David6
  • Sartore-Bianchi, Andrea7
  • Bi, Feng8
  • Yamaguchi, Kensei9
  • Yoshino, Takayuki10
  • Prager, Gerald W11
  • 1 Medical Oncology, Mayo Clinic Cancer Center, Phoenix, AZ.
  • 2 Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL.
  • 3 Department of Oncology, ASAN Medical Center, University of Ulsan, Seoul, South Korea. , (North Korea)
  • 4 Department Clinical Oncology, Clinical Oncology Instituto Alexander Fleming, Buenos Aires, Argentina. , (Argentina)
  • 5 Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC.
  • 6 Department of Cancer Medicine, Gustave Roussy, Université Paris-Saclay, Villejuif, France. , (France)
  • 7 Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy; Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy. , (Italy)
  • 8 Department of Medical Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan, China. , (China)
  • 9 Department of Gastroenterological Chemotherapy, The Cancer Institute Hospital of JFCR, Tokyo, Japan. , (Japan)
  • 10 Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. , (Japan)
  • 11 Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University Vienna, Vienna, Austria. Electronic address: [email protected] , (Austria)
Published Article
Clinical Colorectal Cancer
Publication Date
Mar 01, 2019
DOI: 10.1016/j.clcc.2018.11.002
PMID: 30598357


An increasing number of patients with metastatic colorectal cancer (mCRC) are able to receive 3 or more lines of therapy. Treatments in this setting can include regorafenib (an oral multikinase inhibitor), trifluridine/tipiracil hydrochloride (TAS-102), antibodies that target epidermal growth factor receptor for patients with RAS wild-type tumors (if no prior exposure), and, where approved, anti-programmed cell death protein 1 inhibitors for patients with microsatellite instability-high mCRC. Although guidelines describe the available treatment options, few insights are provided to guide selection and sequencing. In this article, we share expert opinion from diverse geographic regions, to offer guidance for best practice when selecting and managing third-line treatment for mCRC. Various factors, including performance status, age, and tumor sidedness, can be used to guide treatment selection. Biomarkers, such as RAS, BRAF, and microsatellite instability, can be useful for treatment stratification. Management of adverse events, to maintain quality of life, is a key consideration and is crucial to best practice in this setting. Common toxicities associated with third-line treatments are hand-foot skin reaction, fatigue, diarrhea, and cytopenias. Patients who receive third-line and later-line treatments should be monitored for these events, especially during the first 2 cycles. Dose modifications can also be used to manage toxicities and to minimize the effect on quality of life, while maximizing treatment benefit. Clinical trials of emerging agents, new treatment combinations, and novel therapies continue the efforts to improve outcomes for patients with mCRC. Sharing expert opinions on best practice for treatment selection and management can ultimately improve outcomes for patients with mCRC. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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