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

Oncoimmunology. 2020 Jan 22;9(1):1711650. doi: 10.1080/2162402X.2020.1711650. eCollection 2020.

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; PD-1; immune checkpoint blockade; microsatellite instability; neoadjuvant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colorectal Neoplasms* / drug therapy
  • DNA Mismatch Repair / genetics
  • Humans
  • Microsatellite Instability
  • Neoadjuvant Therapy*
  • Programmed Cell Death 1 Receptor / genetics
  • Retrospective Studies

Substances

  • Programmed Cell Death 1 Receptor

Grants and 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].