Emulation of the KEYNOTE177 Trial Using Specialty Oncology Electronic Health Records Databases

This observational trial emulation aims to reproduce the KEYNOTE-177 trial (NCT02563002) using real-world specialty oncology electronic health record data and to assess the concordance between the original and emulated treatment effect estimates for overall survival (OS). KEYNOTE-177 was a phase III, open-label, randomized trial comparing first-line pembrolizumab with 5-fluorouracil-based chemotherapy, with or without bevacizumab or cetuximab, in patients with MSI-H or dMMR metastatic colorectal cancer.

Inclusion Criteria: * Age 18 years or older at first-line study regimen initiation. * Metastatic colorectal cancer documented in a specialty oncology electronic health record. * Initiation of pembrolizumab or 5-fluorouracil-based chemotherapy, with or without bevacizumab or cetuximab, as first-line treatment for metastatic disease. * Confirmed dMMR or MSI-H status for chemotherapy initiators; pembrolizumab initiators were presumed to have dMMR or MSI-H disease based on the treatment indication. * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 when ascertainable in the database. Exclusion Criteria: * Prior systemic treatment for metastatic colorectal cancer. * Chemotherapy within 6 months before study regimen initiation. * Use of an investigational agent within 4 weeks before study regimen initiation. * Active autoimmune disease requiring systemic treatment within 2 years before study regimen initiation. * Known active central nervous system or meningeal metastases. * Prior immune checkpoint inhibitor treatment. * Another primary malignancy within 5 years before study regimen initiation, except nonmelanoma skin cancer or cervical carcinoma in situ.