Abstract
Immune-checkpoint-inhibitors (ICI) are used for adjuvant therapy of squamous cell carcinoma and adenocarcinoma of the esophagogastric junction after prior radiotherapy. The combination of ICI with chemotherapy (CTx) is approved for first-line therapy in a palliative setting (Nivolumab and Ipilimumab) and as second-line option (Nivolumab). Squamous cell carcinoma probably has a higher response rate to ICI and Nivolumab and Ipilimumab are approved as a single therapy for this entity. ICI combined with CTx is approved for metastatic gastric cancer. MSI-H tumors respond well to ICI and can be treated with Pembrolizumab in second line. ICI are only approved for MSI-H/dMMR CRC. Pembrolizumab is a first-line option and Nivolumab combined with Ipilimumab a second-line therapy. Atezolizumab with Bevacizumab is the new first-line therapy of advanced HCC, with additional ICI combinations with positive Phase III studies expected to be approved in the near future. Durvalumab and CTx achieved promising results in a recent Phase 3 study. Pembrolizumab is already EMA-approved as a second-line therapy of MSI-H/dMMR biliary cancer. ICI have not yet achieved a breakthrough in the therapy of pancreatic cancer. FDA-approval exists only for the small subgroup of MSI-H/dMMR tumors. The disinhibition of the immune response by ICI can cause irAE. IrAE most frequently affect the skin, gastrointestinal tract, liver, and endocrine organs. Starting with grade 2 irAE, ICI should be paused, differential diagnosis excluded and if necessary steroid therapy has to be started. Early high-dose use of steroids negatively affects patient outcome. New therapy strategies for irAE are currently tested, such as extracorporeal photopheresis, but larger prospective trials are lacking.
Published Version
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