Neoadjuvant Immunotherapy–Based Systemic Treatment in MMR-Deficient or MSI-High Rectal Cancer: Case Series

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  • 1 UC Davis Comprehensive Cancer Center, Sacramento, California;
  • 2 Loma Linda University Health, Loma Linda Medical Center, Loma Linda, California;
  • 3 Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Health System, Los Angeles, California;
  • 4 City of Hope National Medical Center, Duarte, California;
  • 5 Vanderbilt-Ingram Cancer Center, Nashville, Tennessee;
  • 6 Department of Diagnostic Radiology, UC Davis Medical Center, Sacramento, California;
  • 7 UC Davis Medical Center, California;
  • 8 Department of Surgical Oncology and
  • 9 Department of Colorectal Surgery, UC Davis Medical Center, Sacramento, California;
  • 10 Department of Radiation Oncology, UC Davis Comprehensive Cancer Center, Sacramento, California; and
  • 11 Division of Hematology/Oncology, Department of Medicine, University of California Irvine, Orange, California.
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Treatment options for locally advanced rectal cancer have continued to consist largely of chemotherapy, chemoradiation, and/or surgical resection. For patients who are unable to undergo these therapeutic modalities or who do not to experience a response to them, treatment options are limited. We report 3 cases of mismatch repair–deficient (dMMR) locally advanced adenocarcinoma of the rectum that showed significant response with neoadjuvant immunotherapy–based systemic treatment. The first patient was not eligible for standard therapy because of a history of radiotherapy to the prostate with concurrent comorbidities and therefore received single-agent pembrolizumab. The second patient did not respond to total neoadjuvant chemoradiation and subsequently received combined nivolumab and ipilimumab. The third patient had a known family history of Lynch syndrome and presented with locally advanced rectal cancer and a baseline carcinoembryonic antigen level of 1,566 ng/mL. She was treated using neoadjuvant pembrolizumab and FOLFOX (folinic acid, fluorouracil, oxaliplatin). In this small series, we suggest that single-agent and combined-modality neoadjuvant immunotherapy/chemotherapy appear to be safe and effective treatment options for patients with (dMMR) locally advanced rectal cancer. Our findings encourage further studies to investigate the role of neoadjuvant immunotherapy as a viable treatment strategy in this population.

Submitted December 5, 2019; accepted for publication March 6, 2020.

Disclosures: Dr. Kim has disclosed that he receives grant/research support from Celgene, Astellas, Samumed, Boston Biomedical, Halozyme, EpicentRx, Merck, Oncomed, and Bristol-Myers Squibb; and receives consulting fees from Lilly and Celgene. Dr. Gong has disclosed that he receives consulting fees/honoraria from Amgen and Astellas. Dr. Fakih has disclosed that he receives consulting fees from Array, Amgen, Pfizer Inc., and Bayer; serves on the speaker’s bureau of Amgen and Guardant360; and receives grant/research support from AstraZeneca, Amgen, and Novartis. Dr. Monjazeb has disclosed that he is a scientific advisor for Incyte, Dynavax, and AstraZeneca, and receives grant/research support from Genentech, Merck, Incyte, EMD Serono, Transgene, and Bristol-Myers Squibb. Dr. Dayyani has disclosed that he receives consulting fees from Genentech, Eisai, Exelixis, Array, and Foundation Medicine; serves on the speaker’s bureaus of Amgen, Genentech, Exelixis, Eisai, and Sirtex; and receives grant/research support from Bristol-Myers Squibb, Merck, AstraZeneca, and Taiho. Dr. Cho has disclosed that she receives consulting fees/honoraria from Amgen, Taiho, Astella, Ipsen, Eisai, Exelixis, and Incyte. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: Rahel Demisse, MD, UC Davis Comprehensive Cancer Center, 4501 X Street, Sacramento, CA 95817. Email: rzdemisse@gmail.com
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