Neoadjuvant Immunotherapy Leads to Major Response and Low Recurrence in Localized Mismatch Repair–Deficient Colorectal Cancer
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Background: Our study aimed to evaluate the efficacy and feasibility of neoadjuvant anti–PD-1 treatment for localized mismatch repair–deficient (dMMR) colorectal cancer (CRC). Patients and Methods: The study cohort included patients with localized dMMR CRC who received PD-1 inhibitors as neoadjuvant therapy from 3 medical centers in Southern China. Main eligibility criteria included age between 18 and 75 years, ECOG performance status of 0 or 1, and receipt of ≥2 doses of PD-1 inhibitors. Results: A total of 73 patients were included. Most of the tumors were locally advanced, including 19 (26.0%) T4a and 29 (39.7%) T4b. Most patients (79.5%) received PD-1 inhibitor monotherapy. Objective response per radiologic assessment was achieved in 62 (84.9%) patients, including 17 (23.3%) with complete response (CR) and 45 (61.6%) with partial response, with a median time to response of 9.6 weeks. Patients with T4a/4b disease had a similar response rate as those with T2–3 disease (84.0% vs 85.4%; P=.999). As of writing, a total of 50 patients have undergone surgery. Pathologic CR was achieved in most (57.1%) patients and remained high (59.5%) even among the 38 patients with T4a/4b disease. The 17 patients with CR did not undergo surgery and adopted a watch-and-wait strategy. After a median follow-up of 17.2 months (range, 3.4–45.1 months), the overall median recurrence-free and overall survivals were not reached. Among patients undergoing surgery or achieving CR, the 2-year tumor-specific disease-free and overall survival rates were both 100%. During neoadjuvant treatment, grade 3–4 adverse events occurred in 8 patients; 4 required acute intervention. Severe postoperative complications were recorded in 4 patients, 3 of whom required a second surgery. Conclusions: Neoadjuvant therapy with PD-1 blockade is highly effective for localized dMMR CRC, with an acceptable safety profile and low recurrence rate. This treatment holds promise for becoming the new standard of care for localized dMMR CRCs.
Submitted June 11, 2022; final revision received August 1, 2022; accepted for publication August 1, 2022.
Author contributions: Conception and design: Y.F. Li, X.S. Zhang, Ding. Administrative support: Pan, Ding. Provision of study materials or patients: D.D. Li, J. Xiao, Pan, Y.F. Li, X.S. Zhang, Ding. Collection and assembly of data: B.Y. Xiao, X. Zhang, Cao, Jiang, Kong, Tang, Han, C.Z. Zhang, Mei. Data analysis and interpretation: B.Y. Xiao, X. Zhang, Cao. Manuscript writing: B.Y. Xiao, X. Zhang, Ding. Final approval of manuscript: All authors.
Data availability statement: The authenticity of this article has been validated by uploading the key raw data onto the Research Data Deposit public platform (www.researchdata.org.cn), with the approval RDD number as RDDA2022876429.
Disclosures: The authors have disclosed that they have not received any financial considerations from any person or organization to support the preparation, analysis, results, or discussion of this article.
Funding: Research reported in this publication was supported by the National Natural Science Foundation of China under award numbers 81871971 and 82073159 (P.R. Ding), as well as the Chinese Society of Clinical Oncology under award numbers T-XD2019-073 and Y-Genecast-055 (P.R. Ding).
Disclaimer: This retrospective study was performed in accordance with the Declaration of Helsinki and the Institutional Review Board of Sun Yat-sen University Cancer Center approved to waive informed patient consent due to the observational and noninterventional study (approval number B2020-064-01).
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