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Deficient Pms2, ERCC1, Ku86, CcOI in Field Defects During Progression to Colon Cancer
28:15

Deficient Pms2, ERCC1, Ku86, CcOI in Field Defects During Progression to Colon Cancer

Published on: July 28, 2010

12.8K

Immunotherapy of Colon Cancer

Alexander Stein, Gunnar Folprecht

    Oncology Research and Treatment
    |April 30, 2018
    PubMed

    Insights

    Immune checkpoint inhibitors show efficacy in a subset of colorectal cancers with deficient mismatch repair (dMMR) or microsatellite instability (MSI-H). Combination therapies are needed for the majority of patients without these biomarkers.

    Area of Science:

    • Oncology
    • Immunotherapy
    • Gastrointestinal Cancers

    Background:

    • Immune checkpoint inhibitors targeting PD-1/PD-L1 or CTLA-4 have limited efficacy in unselected colorectal cancer (CRC) patients.
    • Deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) CRC tumors represent a unique subgroup responsive to immunotherapy.

    Purpose of the Study:

    • To review the efficacy of immune checkpoint inhibitors in colorectal cancer.
    • To identify subgroups of colorectal cancer amenable to immunotherapy.
    • To highlight the need for combination strategies in non-dMMR/MSI-H colorectal cancer.

    Main Methods:

    • Review of current clinical trial data and literature on immunotherapy in colorectal cancer.
    • Analysis of patient subgroups based on mismatch repair deficiency (dMMR) and microsatellite instability (MSI-H) status.
    • Evaluation of response rates and durable responses in refractory settings.

    Main Results:

    • PD-1/PD-L1 +/- CTLA-4 inhibition demonstrates significant and durable responses in refractory dMMR/MSI-H colorectal cancer.
    • Ongoing Phase 3 trials are investigating immunotherapy in the adjuvant and first-line metastatic settings for dMMR/MSI-H CRC.
    • The larger non-dMMR/MSI-H subgroup (95% of metastatic cases) currently lacks effective monotherapy options.

    Conclusions:

    • Immunotherapy, specifically PD-1/PD-L1 blockade, is effective in a select group of colorectal cancer patients with dMMR/MSI-H.
    • Combination regimens involving chemotherapy, targeted therapy, local treatments, or other immunotherapies are crucial for the non-dMMR/MSI-H majority.
    • Further research is needed to optimize treatment strategies for all colorectal cancer patients.
    Keywords:
    AdjuvantColorectal cancerImmunotherapyMetastatic

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