Abstract 510MO – pembro MSI-H

In this video Prof Dr Eric Van Cutsem (University Hospitals Leuven) and Prof Dr Scott Kopetz (MD Anderson Cancer Center, Houston, TX, USA) discuss the results of a phase II study evaluating the potential of neoadjuvant pembrolizumab in the treatment of patients with high-risk locally advanced, MSI-H/dMMR colon cancer.

In the presented phase II study, 35 patients with high-risk locally advanced, MSI-H/dMMR colon cancer received 2 cycles of neoadjuvant pembrolizumab after which patients who did not seem to derive any benefit were taken off-study. Patients with a clinical benefit after 2 cycles received an additional 6 cycles of pembrolizumab (200 mg q3w). After 6 months, the treating physician could decide for a surgical resection, or opt for a non-surgical approach consisting of further therapy with pembrolizumab for a total duration of one year.

After a median follow-up of 2.9 years, the ORR in this trial was reported at 82%, with 39.4% of patients obtaining a complete response (CR). All 17 patients who underwent surgery after 6 months of pembrolizumab remained cancer free after 35 months of follow-up. Outcomes were also excellent for the 18 patients for whom the non-surgical treatment option was selected. After a median follow-up of 27.5 months, 14 of them were alive, with an intact organ (2 died, 2 lost to follow-up). In the entire study cohort, the 3-year disease free survival (DFS) rate was reported at 80%, with 93% of patients being alive at the 3-year landmark. Looking at these outcome measures in function of the therapeutic strategy shows a 3-year DFS rate of 83% and 76% for patients in the non-surgical and surgical cohort, respectively. Corresponding rates for OS were 89% and 100%. Interestingly, clearance of circulating tumor DNA (ctDNA) following neoadjuvant pembrolizumab seemed to be predictive for a better DFS and OS.

As such, these findings illustrate the potential of neoadjuvant immune checkpoint inhibition in this setting. Several studies are currently underway to evaluate this strategy in more depth. One of the main questions that will require an answer in the years to come relates to the optimal selection of patients for whom an organ-sparing approach is feasible.