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Validation of biomarkers to predict

response to immunotherapy in

cancer: Volume I - pre-analytical

and analytical validation.

Masucci GV, Cesano A, Hawtin R, et al. Validation of biomarkers to predict response to immunotherapy in
cancer: Volume I - pre-analytical and analytical validation.
Journal for Immunotherapy of Cancer 2016;4:76.

ABSTRACT

Immunotherapies have emerged as one of the most promising approaches to treat patients with cancer. Recently, there have been
many clinical successes using checkpoint receptor blockade, including T cell inhibitory receptors such as cytotoxic T-lymphocyte-
associated antigen 4 (CTLA-4) and programmed cell death-1 (PD-1). Despite demonstrated successes in a variety of malignancies,
responses only typically occur in a minority of patients in any given histology. Additionally, treatment is associated with inflammatory
toxicity and high cost. Therefore, determining which patients would derive clinical benefit from immunotherapy is a compelling clinical
question. Although numerous candidate biomarkers have been described, there are currently three FDA-approved assays based on
PD-1 ligand expression (PD-L1) that have been clinically validated to identify patients who are more likely to benefit from a single-agent
anti-PD-1/PD-L1 therapy. Because of the complexity of the immune response and tumor biology, it is unlikely that a single biomarker
will be sufficient to predict clinical outcomes in response to immune-targeted therapy. Rather, the integration of multiple tumor and
immune response parameters, such as protein expression, genomics, and transcriptomics, may be necessary for accurate prediction of
clinical benefit. Before a candidate biomarker and/or new technology can be used in a clinical setting, several steps are necessary to
demonstrate its clinical validity. Although regulatory guidelines provide general roadmaps for the validation process, their applicability
to biomarkers in the cancer immunotherapy field is somewhat limited. Thus, Working Group 1 (WG1) of the Society for Immunotherapy
of Cancer (SITC) Immune Biomarkers Task Force convened to address this need. In this two volume series, we discuss pre-analytical and
analytical (Volume I) as well as clinical and regulatory (Volume II) aspects of the validation process as applied to predictive biomarkers
for cancer immunotherapy. To illustrate the requirements for validation, we discuss examples of biomarker assays that have shown
preliminary evidence of an association with clinical benefit from immunotherapeutic interventions. The scope includes only those
assays and technologies that have established a certain level of validation for clinical use (fit-for-purpose). Recommendations to meet
challenges and strategies to guide the choice of analytical and clinical validation design for specific assays are also provided.

https://www.ncbi.nlm.nih.gov/pubmed/27895917