New research from Yale Cancer Center reveals that a differential clinical response to pembrolizumab in Lynch-like (mutated) vs methylated microsatellite instability-high (MSI-H) uterine cancer patients, increasing our understanding about the proportion of patients that derive benefit from immune checkpoint blockade.
The findings were published in the journal Cancer Discovery.
Defects in DNA mismatch repair (MMR) genes are common in tumors and are usually caused by an inherited defect in the function of one of the MMR genes. The main characteristic of these tumors is that they are associated with genome-wide instability and the progressive accumulation of mutations, especially in regions of simple repetitive DNA sequences known as microsatellites, resulting in microsatellite instability (MSI) high (MSI-H) tumors. Cancers deficient in MMR gene function (dMMR) are prevalent in many solid tumors and account for up to 30% of all uterine tumors, 20% of gastric cancer, and 15% of colorectal cancer, among others.
A phase 2 clinical trial of the PD-1 inhibitor pembrolizumab provided a partial answer to this question. The study was conducted in 24 patients with mismatch repair-deficient (MMRd) endometrial cancer and it was found that responses to pembrolizumab in Lynch-like (mutated) patients were stronger and significantly more lasting than those experienced by methylated MSI-H uterine cancer patients.
