On indications for cancer immunotherapy: A review of current practice for immunology-based indications

Abstract

Knowledge of tumor immunology and immune escape mechanisms was the basis for developing immune checkpoint inhibitors (ICI) for cancer therapy. These target and block checkpoint molecules commonly implicated in tumor immune escape by overexpression, such as PD-1, its ligand, PD-L1 or CTLA-4. Use of ICIs has been approved mostly for treatment of advanced disease, some without any requirement for checkpoint overexpression on tumors. The objectives of this review is to investigate how common lack of immunological biomarker requirement is, and for therapies with such a requirement, the reason for and the importance of overexpression, as well as reviewing what challenges clinicians face in this field.

Performing two related semi-systematic reviews, all currently approved cancer antibody therapies categorized by The Norwegian Medicines Manual for Health personnel were reviewed to investigate indications for ICI therapy, and a literature review on current practice in their use was performed to investigate reasons for the discrepant requirements in indications. Approved therapies were also screened for antibodies with similar specificity and indications, where one was immunology based and the other was not, to investigate whether there were discrepancies in efficacy based on PD-L1 expression for similar antibodies.