Abstract
Gastrointestinal (GI) cancers are a group of highly aggressive malignancies with a huge disease burden worldwide. There is clearly a significant unmet need for new drugs and therapies to further improve the treatment outcomes of GI malignancies. Immunotherapy is a novel treatment strategy that is emerging as an effective and promising treatment option against several types of cancers. CTLA-4 and PD-1 are critical immune checkpoint molecules that negatively regulate T cell activation via distinct mechanisms. Immune checkpoint blockade with antibodies directed against these pathways has already shown clinical efficacy that has led to their FDA approval in the treatment of several solid tumors including melanoma, non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, and head and neck cancer. This review will summarize the current clinical progress of modern immunotherapy in the field of GI tumors, with a special focus on immune checkpoint blockade
Highlights
Gastrointestinal (GI) cancers are a group of highly aggressive malignancies with a huge disease burden worldwide
The median progression-free survival (PFS) was not reached for MMR-deficient Colorectal cancer (CRC) and was 2.4 months for MMR-proficient CRC (HR = 0.135; 95% CI, 0.043 to 0.191; P = 0.0001)
These results suggest that MMR-deficient CRC tumors receive durable benefit from anti-PD-1 therapy
Summary
Gastrointestinal (GI) cancers are a group of highly aggressive malignancies with a huge disease burden worldwide. No association was observed between response and higher PD-L1 expression on tumor cells, as assessed with the clinical trial assay In another similar multi-cohort phase Ib trial, single-agent pembrolizumab was evaluated in PDL1-positive advanced solid tumors (KEYNOTE-028, NCT02054806). Single-agent pembrolizumab exhibited a manageable toxicity profile with 17% of the patients experiencing grade 3 TRAEs. The encouraging clinical activity observed in these studies formed the basis for larger phase II and III studies of anti-PD-1 therapies in gastric, esophageal, and GEJ cancers. KEYNOTE-062 is another randomized phase III study containing three arms which will compare the safety and efficacy of pembrolizumab monotherapy, versus 5FU plus cisplatin, versus all three agents combined together in the firstline treatment of PD-L1-positive advanced gastric or GEJ adenocarcinoma (NCT02494583). Novel treatment strategies such as immunotherapy are being evaluated to further improve the outcomes of this disease
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