PD-1 blockade in neoadjuvant setting of DNA mismatch repair-deficient/microsatellite instability-high colorectal cancer

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.

KEYWORDS:

• Colorectal cancer
• microsatellite instability
• neoadjuvant
• PD-1
• immune checkpoint blockade

Disclosure of Potential Conflicts of Interest

The authors declare no potential conflicts of interest.

Author Contributions

All authors listed have contributed sufficiently to the project to be included as authors, and all those who are qualified to be authors are listed in the author byline. All authors have read and approved the article. The authors of this study have not published or submitted any related articles from this study. This article is not under consideration elsewhere.

Data

All data in our study have been recorded at Sun Yat-sen University Cancer Center for future reference (number RDDA2019001099).

Ethical issues

All the enrolled patients approved to use PD-1 blockade as a neoadjuvant therapy before the treatment. And this retrospective study has received the full approval of the ethics committee of the Sun Yat-Sen University Cancer Center, China.

Statistical analysis

All continuous data were expressed as median with the range. All discrete variables were shown as counts and percent. The software program SPSS version 19 (SPSS Inc., Chicago, IL, USA) was used for statistical analyses.

Supplementary Material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [No. 81871971 to Peirong Ding], the Science and Technology Planning Project of Guangzhou City of China [No. 201803010117 to Peirong Ding], 5010 Plan of Sun Yat Sen University [No. 2014013 to Peirong Ding], National Key R&D Program of China [No.2017YFC0906202 to Zhizhong Pan], the Science and Technology Planning Project of Guangzhou City of China [No. 201803040019 to Desen Wan], the Science and Technology Planning Project of GuangDong Province of China [No. 2013B090800047 to Zhizhong Pan].