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Perspectives on Treatment of Metastatic Colorectal Cancer with Immune Checkpoint Inhibitor Therapy.

Publication ,  Journal Article
Morse, MA; Hochster, H; Benson, A
Published in: Oncologist
January 2020

Despite lengthening survival, death rates from metastatic colorectal cancer (CRC) remain unacceptably high, with a bright spot being the demonstration of durable responses in patients with CRC who have mismatch repair-deficient (dMMR) and/or microsatellite instability-high (MSI-H) tumors and are treated with immune checkpoint inhibitor therapy. Nivolumab and pembrolizumab, as well as nivolumab in combination with low-dose ipilimumab-all checkpoint inhibitors-are currently approved by the U.S. Food and Drug Administration (FDA) for patients with MSI-H/dMMR metastatic CRC that progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. Nonetheless, there are a number of questions and considerations in the use of these checkpoint inhibitor therapies. Using a question-and-answer format, this review summarizes the scientific rationale for immune checkpoint inhibitor therapy in CRC, including the effects of tumor factors such as genetic aberrations and mutational load on the immune response, particularly in patients with MSI-H/dMMR disease. We discuss response patterns, response criteria, and immune-related adverse events using findings from published efficacy and safety data of immune checkpoint inhibitor therapy in metastatic CRC. We also discuss issues surrounding treatment sequencing, incorporating approved checkpoint inhibitors into the current treatment paradigm, and the multiple investigational strategies that may optimize immunotherapy for advanced CRC in the future, including novel combination therapies. IMPLICATIONS FOR PRACTICE: Colorectal cancer (CRC) is the third most common cancer in the U.S. Despite advances in chemotherapy, survival remains poor for patients with metastatic CRC. Certain immunotherapy agents have demonstrated long-lasting responses in previously treated patients with immune-responsive microsatellite instability-high/mismatch repair-deficient metastatic CRC, leading to U.S. Food and Drug Administration approval of the immune checkpoint inhibitors nivolumab (with or without low-dose ipilimumab) and pembrolizumab in this population. Combination therapy (e.g., nivolumab with low-dose ipilimumab) has demonstrated numerically higher response rates and improved long-term clinical benefit relative to anti-programmed death-1 monotherapy. Ongoing trials are evaluating immunotherapy in the broader CRC population and novel combinations to optimize immunotherapy for advanced CRC.

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Published In

Oncologist

DOI

EISSN

1549-490X

Publication Date

January 2020

Volume

25

Issue

1

Start / End Page

33 / 45

Location

England

Related Subject Headings

  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Immunotherapy
  • Humans
  • Colorectal Neoplasms
  • Antibodies, Monoclonal
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
 

Citation

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Morse, M. A., Hochster, H., & Benson, A. (2020). Perspectives on Treatment of Metastatic Colorectal Cancer with Immune Checkpoint Inhibitor Therapy. Oncologist, 25(1), 33–45. https://doi.org/10.1634/theoncologist.2019-0176
Morse, Michael A., Howard Hochster, and Al Benson. “Perspectives on Treatment of Metastatic Colorectal Cancer with Immune Checkpoint Inhibitor Therapy.Oncologist 25, no. 1 (January 2020): 33–45. https://doi.org/10.1634/theoncologist.2019-0176.
Morse MA, Hochster H, Benson A. Perspectives on Treatment of Metastatic Colorectal Cancer with Immune Checkpoint Inhibitor Therapy. Oncologist. 2020 Jan;25(1):33–45.
Morse, Michael A., et al. “Perspectives on Treatment of Metastatic Colorectal Cancer with Immune Checkpoint Inhibitor Therapy.Oncologist, vol. 25, no. 1, Jan. 2020, pp. 33–45. Pubmed, doi:10.1634/theoncologist.2019-0176.
Morse MA, Hochster H, Benson A. Perspectives on Treatment of Metastatic Colorectal Cancer with Immune Checkpoint Inhibitor Therapy. Oncologist. 2020 Jan;25(1):33–45.

Published In

Oncologist

DOI

EISSN

1549-490X

Publication Date

January 2020

Volume

25

Issue

1

Start / End Page

33 / 45

Location

England

Related Subject Headings

  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Immunotherapy
  • Humans
  • Colorectal Neoplasms
  • Antibodies, Monoclonal
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis