Matthew Farren, PhD, post-doctoral fellow, Winship Cancer Institute, Emory University, discusses findings from a multicenter, single-arm phase II clinical trial evaluating the combination of pembrolizumab (Keytruda) and modified leucovorin/5-fluorouracil/oxaliplatin (mFOLFOX6) in patients with advanced colorectal cancer (CRC).

Results showed that there were 8 clinical responses to the combination, 7 of which were partial and 1 of which was complete by RECIST criteria. There were 16 partial responses by immune-related response criteria. The progression-free survival (PFS) in these patients was approximately 1 year. Overall survival (OS) had yet to be reported. At the time of data cutoff at about 17.5 months, 76% of patients were still alive, says Farren.

Biomarkers of response were also examined. T-cell checkpoint molecules were identified and showed that CD4 and CD8 T cell expression was negatively associated with clinical response, he adds. Patients who had higher levels of LAG-3 on their CD4 and CD8 T cells at baseline were less likely to have a partial or complete response, Farren explains. Additionally, patients who expressed cytokines at higher than median levels were less likely to experience a clinical response.

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Findings 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.

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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.
 

Matthew Farren, PhD

Articles

Findings for Pembrolizumab Plus mFOLFOX6 in Advanced CRC

Rationale for Pembrolizumab Plus mFOLFOX6 in Advanced CRC