P0320 - Efficacy and Safety of Neoadjuvant Anti-PD1/PDL-1 for MSI/dMMR for Locally Advanced Colorectal Cancer: A Systematic Review and Meta-Analysis

Keerthi Balaji Babu Naidu, ¹, Ananya Prasad, ², Vinay Chandramouli Bellur, ¹, Omar Oudit, DO³, Pavan Kumara Kasam Shiva, ⁴, Vibhav MS, ⁴, Shradha Chervittara Karaveetil, ², Deepika A, ⁴, Swaroop Raj Varma K R, ⁴, Vardhini Ganesh Iyer, ⁵, Rishikesh R. Magaji, ⁵, Gaurav Jayadev, ⁶, Trisha Chandra Mohan, ⁵, Druvadeep Srinivas, ⁷, Allama Prabhu N S, ⁸, Sravani Bhavanam, ⁹, Prakriti Ramamurthy, MBBS, MD¹⁰
1Ramaiah medical college, Bangalore, Karnataka, India; 2ramaiah medical college, Bangalore, Karnataka, India; 3Brookdale University Hospital Medical Center, Brooklyn, NY; 4bangalore medical college and research institute, Bangalore, Karnataka, India; 5BGS Global Institute of Medical Sciences, Bangalore, Karnataka, India; 6basaveshwara medical college and hospital, Bangalore, Karnataka, India; 7rajarajeshwari medical college & hospital, Bangalore, Karnataka, India; 8Bangalore Medical College and Research Institute, Bangalore, Karnataka, India; 9Brookdale University Hospital Medical Center, Bangalore, Karnataka, India; 10University of Massachusetts Chan Medical School - Baystate Health, Springfield, MA

Introduction:

Colorectal cancer(CRC) is the third most common cancer worldwide. Microsatellite instability-high (MSI-H) and mismatch repair -deficient(dMMR) are distinct immunogenic subtypes of CRC. Treatment modalities for CRC include chemoradiation, surgery, immunotherapy etc. Evidences suggest that most patients with MSI-H/dMMR do not respond well to neoadjuvant chemoradiation. However, recent trials with neoadjuvant immunotherapy, particularly anti-PD1/PDL1 have shown promising results with respect to patient outcomes and survival. This meta analysis thereby aims to evaluate the safety and efficacy of neoadjuvant anti-PD1/PDL1 in patients with MSI-H/dMMR locally advanced CRC.

Methods:

The review conducted follows the PRISMA guidelines. PUBMED, Google Scholar and Science-Direct, were extensively searched using a comprehensive search term to identify and retrieve available articles. The articles that included the assessment of the pathological and clinical response rate (pCRR and cCRR), Rate of R0 resection and Objective Response Rate (ORR) were considered.

The data was analysed using the Meta, Metadata and the Metafor packages of R Studio. The pooled proportions of Rate of R0 Resection, pCRR and cCRR and ORR were analysed. The Mantel-Haenszel method and the Inverse variance method were utilised to analyse the odds ratio. The I^2 test was used to assess the heterogeneity of the studies.

Results:

The analysis included a total of 16 studies with 427 patients undergoing Anti PD1 Therapy for CRC. The Pooled Rate of R0 Resection was 97% ((0.84;0.99), p=0.0487 ,I^2 = 52.6%) and the Pooled Pathological Complete Response Rate was analysed to be 62% ((0.50;0.73), p< 0.0001 ,I^2 = 77.2%). The Pooled Clinical Complete Response Rate was calculated to be 31% ((0.18;0.47), p=0.0002 ,I^2 = 77.2%). The Objective Response Rate was found to be 76%  ((0.65;0.84), p=0.0080 ,I^2 = 58.1%)

Discussion:

Our study highlights the efficacy of Anti PD1 in patients with MSI-H/dMMR locally advanced CRC due to high rates of R0 Resection, Pathological Complete Response and Objective Response Rate. The study also shows that the Clinical Response Rates were comparatively lower in contrast to the Pathological Response Rate.


Figure: The above figure shows the Pooled Proportions for Rate of R0 Resection and Pathological Complete Clinical Response


Figure: The above figure shows the Pooled Proportions for Clinical Complete Clinical Response and Objective Response Rate

Disclosures:
Keerthi Balaji Babu Naidu indicated no relevant financial relationships.
Ananya Prasad indicated no relevant financial relationships.
Vinay Chandramouli Bellur indicated no relevant financial relationships.
Omar Oudit indicated no relevant financial relationships.
Pavan Kumara Kasam Shiva indicated no relevant financial relationships.
Vibhav MS indicated no relevant financial relationships.
Shradha Chervittara Karaveetil indicated no relevant financial relationships.
Deepika A indicated no relevant financial relationships.
Swaroop Raj Varma K R indicated no relevant financial relationships.
Vardhini Ganesh Iyer indicated no relevant financial relationships.
Rishikesh R. Magaji indicated no relevant financial relationships.
Gaurav Jayadev indicated no relevant financial relationships.
Trisha Chandra Mohan indicated no relevant financial relationships.
Druvadeep Srinivas indicated no relevant financial relationships.
Allama Prabhu N S indicated no relevant financial relationships.
Sravani Bhavanam indicated no relevant financial relationships.
Prakriti Ramamurthy indicated no relevant financial relationships.

Keerthi Balaji Babu Naidu, ¹, Ananya Prasad, ², Vinay Chandramouli Bellur, ¹, Omar Oudit, DO³, Pavan Kumara Kasam Shiva, ⁴, Vibhav MS, ⁴, Shradha Chervittara Karaveetil, ², Deepika A, ⁴, Swaroop Raj Varma K R, ⁴, Vardhini Ganesh Iyer, ⁵, Rishikesh R. Magaji, ⁵, Gaurav Jayadev, ⁶, Trisha Chandra Mohan, ⁵, Druvadeep Srinivas, ⁷, Allama Prabhu N S, ⁸, Sravani Bhavanam, ⁹, Prakriti Ramamurthy, MBBS, MD¹⁰. P0320 - Efficacy and Safety of Neoadjuvant Anti-PD1/PDL-1 for MSI/dMMR for Locally Advanced Colorectal Cancer: A Systematic Review and Meta-Analysis, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.