There has been quite a bit of excitement in oncology in the last decade surrounding immunotherapy agents and the amazing results we have seen in a variety of difficult to treat malignancies. These results have included disease processes ranging from lung cancer to lymphomas. We are beginning to see these types of outcomes in the world of GI malignancies, and are finding hope for those with an otherwise poor prognosis.
Results from a study presented at the recent GI Cancer Symposium looked at the association of PD-1 and PD-L1 expression on mismatch repair status and prognosis in patients with esophageal and gastric adenocarcinoma. MSI-high or MMR-deficient tumors are most often found in colorectal cancer, endometrial cancer, and other GI cancers. This study examined patients with resectable esophageal and gastric (EG) cancers, a population with historically poor prognosis. The study focused on patients who were chemotherapy and radiation therapy naive.
Expression of PD-L1 has been shown to have some predictive power on response to treatment in certain malignancies. Expression of PD-L1 along with MMR status have been shown to be acceptable biomarkers to assess response to immune-modulating therapies, however they do not seem to have a prognostic value in esophageal and gastric cancers. The goal of this particular study was to examine PD-L1 expression in tumor cells (TC) and PD-L1 and PD-1 expression in tumor infiltrating immune cells (TIC) in EG adenocarcinoma. They found that PD-L1 expression in TC and TIC was associated with MMR deficiency. However neither MMR status nor PD-L1 status in TC were prognostic.
Interestingly, high PD-1 levels of 10%, and PD-L1 levels of greater than 50% in TIC were significantly associated with a prolonged OS. A high PD-L1 was found to have a prolonged OS independent of other prognostic factors and MMR status. The prognostic value was only seen in MMR proficient tumors and was found to be similar in esophageal and gastric tumors. The study concluded that high expressions of PD-L1 were associated with MMR deficiency in EG malignancies. High PD-L1 expression in TIC was found to significantly prolong survival, especially in MMR proficient tumors.
Immunotherapy is changing the way we view oncology and how we approach treatment paradigms across the board. As we continue to examine these tumor markers and immunotherapeutic agents we can expect to see more ways in which to understand prognostic factors and further personalize our therapies.