Systematic Review of Neoadjuvant Immunotherapy for Mismatch Repair Deficient Locally Advanced Colon Cancer: An
Anthony Loria1, Allison M Ammann2, Olugbenga O Olowokure3
1Department of Surgery, University of Rochester Medical Center, Rochester, New York.
Background:
In April 2023, the National Comprehensive Cancer Network endorsed neoadjuvant immunotherapy for select patients with nonmetastatic mismatch repair deficient colon cancer. Approximately 15% of incident colon cancers are mismatch repair deficient, resulting in a distinct molecular subtype with high microsatellite instability that is responsive to immune checkpoint inhibition.
Objective:
To describe the existing evidence supporting neoadjuvant immunotherapy for mismatch repair deficient, microsatellite unstable nonmetastatic colon cancer.
Data Sources:
A medical librarian performed PubMed, Embase, and Web of Science searches most recently on April 24, 2023. The PubMed search was re-run on September 26, 2023, to identify any additional studies published between April 24 and September 26, 2023.
Study Selection:
Two authors screened titles and abstracts in the published studies. The inclusion criteria were 1) English language, 2) adults with primary cancer of the colon, 3) nonmetastatic disease, 4) neoadjuvant immunotherapy, and 5) reporting on 10 or more cases.
Intervention:
Neoadjuvant immunotherapy.
Main Outcome Measures:
Safety (grade 3+ treatment-related adverse events) and efficacy (complete pathologic responses).
Results:
From 7691 studies identified, 6370 were screened and 8 were included. Various agents, dosing regimens, and treatment durations were used, with durations of immunotherapy ranging from 1 to 16 cycles. Complete R0 resections were consistently achieved in 98% to 100% of resections. Of patients who received neoadjuvant immunotherapy and underwent resection, 50% to 91% had ypT0N0 pathology. The safety profiles were generally favorable, with grade 1 to 2 treatment-related adverse events (mostly immune-related) during immunotherapy reported in 22.2% to 70% of patients. Postoperative complications after neoadjuvant immunotherapy were reassuring, with no severe complications reported.
Limitations:
Small number of heterogeneous and uncontrolled studies precluding a meta-analysis.
Conclusions:
Neoadjuvant immune checkpoint inhibition is associated with high rates of pathologic complete responses in locally advanced colon cancer. The literature is limited, particularly for postoperative outcomes, and more studies are needed to understand the safety and positioning of these regimens in the neoadjuvant context.
Insights
Neoadjuvant immunotherapy shows high pathologic complete response rates in mismatch repair deficient colon cancer. Further research is needed to confirm safety and optimal use in the neoadjuvant setting.
Area of Science:
- Oncology
- Immunotherapy
- Gastrointestinal Cancers
Background:
- Mismatch repair deficient (dMMR) colon cancer, a distinct molecular subtype with high microsatellite instability, is responsive to immune checkpoint inhibition.
- The National Comprehensive Cancer Network now endorses neoadjuvant immunotherapy for select patients with nonmetastatic dMMR colon cancer.
Purpose of the Study:
- To review existing evidence on neoadjuvant immunotherapy for dMMR, microsatellite unstable, nonmetastatic colon cancer.
- To assess the safety and efficacy of this treatment approach.
Main Methods:
- Searches of PubMed, Embase, and Web of Science were conducted up to September 26, 2023.
- Included studies were in English, focused on adults with nonmetastatic colon cancer receiving neoadjuvant immunotherapy, and reported on at least 10 cases.
- Safety and complete pathologic responses were the primary outcome measures.
Main Results:
- Eight studies involving various immunotherapy agents, regimens, and durations were included.
- High rates of complete R0 resection (98-100%) were achieved.
- Pathologic complete response (ypT0N0) ranged from 50% to 91% in resected patients, with generally favorable safety profiles and low rates of severe postoperative complications.
Conclusions:
- Neoadjuvant immune checkpoint inhibition demonstrates high pathologic complete response rates in locally advanced colon cancer.
- The current literature is limited by small, heterogeneous, and uncontrolled studies, precluding meta-analysis.
- More research is essential to fully understand the safety and optimal role of these regimens in neoadjuvant treatment.
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