Rationale for Pembrolizumab Plus mFOLFOX6 in Advanced CRC

Matthew Farren, PhD, post-doctoral fellow, Winship Cancer Institute, Emory University, discusses the rationale behind the combination of pembrolizumab (Keytruda) and modified leucovorin/5-fluorouracil/oxaliplatin (mFOLFOX6) in patients with advanced colorectal cancer (CRC).

Response to PD-1 inhibition in CRC has been varied, Farren says. Patients with microsatellite instability-high (MSI-H) tumors tend to respond better than those who have microsatellite stable (MSS) disease, which is attributed to the lower neoantigen burden in those with MSS tumors as compared to those with MSI-H tumors. Currently, pembrolizumab is only approved for use in patients with CRC who have unresectable or metastatic MSI-H or mismatch repair deficient tumors that have progressed after prior treatment.

The combination of pembrolizumab and mFOLFOX6 is being evaluated in a multicenter, single-arm phase II clinical trial. The hypothesis for this trial is that the chemotherapy might potentiate an immune response that can then be acted on by the pembrolizumab to enhance antitumor activity. Farren explains that the rationale for using mFOLFOX6 is that it has several components that have shown to cause immunogenic cell death.