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Published on: July 25, 2020
PD-1 blockade in neoadjuvant setting of DNA mismatch repair-deficient/microsatellite instability-high colorectal
Ding-Xin Liu1,2, Dan-Dan Li1,3, Wan He4
1State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
Abstract:
Background: Although PD-1 blockade has significantly improved the survival of metastatic colorectal cancer with DNA Mismatch Repair-Deficient/Microsatellite Instability-High (MSI-H), the data on neoadjuvant setting is limited. Methods: In this retrospective study, we enrolled eight patients with advanced MSI-H colorectal cancer from three hospitals. Four patients are locally advanced and four are metastatic. All the patients received at least two doses of PD-1 antibody with or without chemotherapy as neoadjuvant therapy. The aim of the present study was to evaluate the short-term efficacy and toxicities of this strategy. Results: All the enrolled eight patients had a major response in imaging and/or pathological evaluation. Five of the seven resected patients were evaluated as pathological complete response. One patient without surgery has a clinical complete response (cCR) tumor response. Conclusions: Neoadjuvant PD-1 blockade induced tumor regression with a major clinical and pathological response in advanced dMMR/MSI-H colorectal cancer. Further studies are required to evaluate the long-term effect of this strategy.
Insights
Neoadjuvant PD-1 blockade shows promising results for advanced DNA Mismatch Repair-Deficient/Microsatellite Instability-High colorectal cancer, inducing significant tumor regression. Further research is needed to confirm long-term efficacy and safety.
Area of Science:
- Oncology
- Immunotherapy
- Gastrointestinal Oncology
Background:
- PD-1 blockade has improved survival in metastatic colorectal cancer (CRC) with DNA Mismatch Repair-Deficient/Microsatellite Instability-High (dMMR/MSI-H) tumors.
- Limited data exists on the efficacy of PD-1 blockade in the neoadjuvant setting for advanced dMMR/MSI-H CRC.
Purpose of the Study:
- To evaluate the short-term efficacy and toxicities of neoadjuvant PD-1 blockade in patients with advanced dMMR/MSI-H colorectal cancer.
- To assess tumor response through imaging and pathological evaluation after neoadjuvant therapy.
Main Methods:
- Retrospective study involving eight patients with advanced dMMR/MSI-H colorectal cancer (four locally advanced, four metastatic).
- All patients received at least two doses of PD-1 antibody, with or without chemotherapy, as neoadjuvant therapy.
- Evaluation of short-term efficacy and toxicities.
Main Results:
- All eight patients demonstrated a major response on imaging and/or pathological evaluation.
- Five of seven resected patients achieved pathological complete response.
- One non-surgically treated patient achieved a clinical complete response (cCR).
Conclusions:
- Neoadjuvant PD-1 blockade effectively induces tumor regression in advanced dMMR/MSI-H colorectal cancer.
- The strategy resulted in major clinical and pathological responses.
- Further studies are warranted to determine the long-term effects of this neoadjuvant approach.
