S370 Efficacy and Safety of Neoadjuvant Anti-PD1/PDL-1 for MSI/dMMR for Locally Advanced Colorectal Cancer: A Systematic Review and Meta-Analysis

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. Evidence 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, 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 utilized to analyze the odds ratio. The I2 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, I2 = 52.6%) and the pooled pathological complete response rate was analyzed to be 62% ([0.50; 0.73], P < 0.0001, I2 = 77.2%). The pooled clinical complete response rate was calculated to be 31% ([0.18; 0.47]; P = 0.00020, I2 = 77.2%). The ORR was found to be 76% ([0.65; 0.84], P = 0.0080, I2 = 58.1%). Conclusion: 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.