Sustained Disease Control in Immune Checkpoint Blockade Responders with Microsatellite Instability-high Colorectal Cancer after Treatment Termination

Authors

Kristen Simmons
Jane V Thomas
Kaysia Ludford
Jason A Willis
Victoria S Higbie
Kanwal P S Raghav
Benny Johnson
Arvind Dasari
Bryan K Kee
Christine M Parseghian
Michael S Lee
Phat H Le
Maria P Morelli
John Paul Shen
Alisha Bent
Eduardo Vilar
Robert A Wolff
Scott Kopetz
Michael J Overman
Van Karlyle Morris

Publication Date

12-11-2023

Journal

Cancer Research Communications

Abstract

Immune checkpoint inhibitors improve survival in patients with mismatch repair deficiency/microsatellite instability-high (MSI-H) colorectal cancer. The recurrence outcomes following discontinuation of immunotherapy after prolonged disease control have not been definitively reported in large series. Records from patients with advanced MSI-H colorectal cancer from The University of Texas - MD Anderson Cancer Center who received immunotherapy between 2014 and 2022 and stopped after prolonged clinical benefit were reviewed. Median progression-free and overall survival were estimated. Associations between the event of recurrence and coexisting mutations (KRAS/NRAS, BRAFV600E), metastatic organ involvement (lung, liver, lymph node, or peritoneum), metastatic timing (synchronous vs. metachronous), prior immunotherapy [anti-PD-(L)1 alone or in combination with anti-CTLA antibodies], etiology of MSI status (sporadic vs. hereditary non-polyposis colorectal cancer), and duration of immunotherapy were assessed. Sixty-four patients with MSI-H colorectal cancer without progression on immunotherapy were reviewed. Of these 48 and 16 received anti-PD(L)1 antibody alone or in combination with anti-CTLA-4 antibody, respectively. Median exposure to immunotherapy was 17.6 months (range, 1.3-51.9). After a median follow-up of 22.6 months (range, 0.3-71.7) after stopping immunotherapy, 56 of 64 patients (88%) remained without disease progression. Lung metastases were associated with recurrence/progression (OR, 6.1; P = 0.04), but coexisting mutation, primary tumor sidedness, and immunotherapy were not. These data provide a retrospective, single-institution analysis that showed that most patients with advanced MSI-H colorectal cancer do not recur after treatment cessation, regardless of the reason for stopping treatment or a variety of patient and disease features, supporting an optimistic prognosis of sustained disease control.

Keywords

Humans, Immune Checkpoint Inhibitors, Retrospective Studies, Microsatellite Instability, Colonic Neoplasms, Colorectal Neoplasms

Comments

Supplementary Material

Data Availability Statement

PMID: 38085001

DOI

10.1158/2767-9764.CRC-23-0340

PMID

38085001

PMCID

PMC10712284

PubMedCentral® Posted Date

December 2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes