Neoadjuvant Immune Checkpoint Inhibitor Therapy for Patients With Microsatellite Instability-High Colorectal Cancer: Shedding Light on the Future


Sahin I. H., Zhang J., Saridogan T., Gorantla V., Rhree J., Malhotra M., ...More

JCO oncology practice, vol.19, no.5, pp.251-259, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 19 Issue: 5
  • Publication Date: 2023
  • Doi Number: 10.1200/op.22.00762
  • Journal Name: JCO oncology practice
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CINAHL, EMBASE, MEDLINE
  • Page Numbers: pp.251-259
  • Hacettepe University Affiliated: Yes

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment paradigm of mismatch repair-deficient/microsatellite instability-high (MMMR-D/MSI-H) colorectal cancer (CRC). Unique molecular features of MMR-D/MSI-H CRC with frameshift alterations, which result in mutation-associated neoantigen (MANA) generation, create an ideal molecular framework for MANA-driven T-cell priming and antitumor immunity. These biologic characteristics of MMR-D/MSI-H CRC resulted in rapid drug development with ICIs for patients with MMR-D/MSI-H CRC. Observed deep and durable responses with the use of ICIs in advanced-stage disease have stimulated the development of clinical trials with ICIs for patients with early-stage MMR-D/MSI-H CRC. Most recently, neoadjuvant dostarlimab monotherapy for nonoperative management of MMR-D/MSI-H rectal cancer and neoadjuvant NICHE trial with nivolumab and ipilimumab for MMR-D/MSI-H colon cancer resulted in groundbreaking results. Although nonoperative management of patients with MMR-D/MSI-H rectal cancer with ICIs will potentially define our current therapeutic approach, therapeutic goals of neoadjuvant ICI therapy for patients with MMR-D/MSI-H colon cancer may differ given that nonoperative management has not been well established for colon cancer. Herein, we overview recent advancements in ICI-based therapies for patients with early-stage MMR-D/MSI-H colon and rectal cancer and elaborate on the future treatment paradigm of this unique subgroup of CRC.