Atezolizumab in Patients With MSI-h/MMR-D Stage II High Risk and Stage III Colorectal Cancer Ineligible for Oxaliplatin

The current standard of care for adjuvant treatment of oxaliplatin-ineligible patients with stage III dMMR colon cancer is fluoropyrimidine monotherapy. In the COLOPREDICT registry, the 3 years DFS rate for such patients \>70 years of age is 63% (95%CI: 53-75%). In contrast to patients with mismatch repair proficient (pMMR) colon cancer, however, it is not established whether patients with stage III dMMR colon cancer benefit from adjuvant fluoropyrimidine monotherapy at all. For patients with stage II colon cancer in an otherwise identical setting, there is no indication for adjuvant treatment due to a lack of clinical benefit compared to surgery alone. Clinical results suggests a similar situation for stage III malignancy. Siwemilar to other checkpoint inhibitors (CPI), the PD-L1 antibody atezolizumab demonstrated impressive activity and good tolerability in patients with metastatic dMMR CRC. Recently, the randomized phase III Keynote-177 trial was presented. In Keynote-177, patients with dMMR metastatic CRC were randomized to the PD-1 antibody pembrolizumab or to chemotherapy (mFOLFOX6 or FOLFIRI with or without bevacizumab or cetuximab as per Investigator's choice). Pembrolizumab treatment resulted in a statistically significant prolongation of Progression-free survival . In addition, side effects were lower with pembrolizumab and quality of life was improved compared to conventional chemotherapy. Thus, pembrolizumab will become the new standard of care in patients with dMMR metastatic CRC in first-line therapy.