Journal Article

Monitoring immune-checkpoint blockade: response evaluation and biomarker development

Ramaiya, Nikhil H., Hatabu, Hiroto, Nishino, Mizuki, Hodi, F. Stephen

2017

Overview

Key Points A subset of patients receiving immune-checkpoint inhibitor therapy develop unconventional response patterns (termed 'pseudoprogression'), in which tumour burden decreases after an initial increase, or during or after the appearance of new lesions The evaluation of pseudoprogression provides new challenges in treatment monitoring and therapeutic decision-making because it cannot be evaluated with the existing response-evaluation criteria The establishment of a standardized strategy to evaluate immune-related responses in patients receiving immune-checkpoint inhibitors is extremely important In addition, the development of robust biomarkers to assist prediction of response and clinical benefits of immune-checkpoint inhibitor therapy is essential to further advance the field as precision immuno-oncology The therapeutic activity of immune-checkpoint inhibitors is the result of a complex interplay between multiple factors in the tumour, tumour microenvironment, and immune system, requiring a collaborative approach to translate the emerging knowledge into the clinical context Patients receiving anticancer therapies based on immune-checkpoint blockade (ICB) often experience clinical benefits from such treatments, but unconventional patterns of response can be observed, emphasizing the importance of using a specific approach to evaluating responses to immunotherapy. Herein, the authors review the biological mechanisms underlying the response patterns associated with ICB, describe strategies for the assessments of such responses, and highlight the ongoing efforts to identify biomarkers to guide treatment with ICB. Cancer immunotherapy using immune-checkpoint blockade (ICB) has created a paradigm shift in the treatment of advanced-stage cancers. The promising antitumour activity of monoclonal antibodies targeting the immune-checkpoint proteins CTLA-4, PD-1, and PD-L1 led to regulatory approvals of these agents for the treatment of a variety of malignancies. Patients might experience clinical benefits from treatment with these agents, despite unconventional patterns of tumour response that can be misinterpreted as disease progression, warranting a new, specific approach to evaluate responses to immunotherapy. In addition, biomarkers that can predict responsiveness to ICB are being extensively investigated to further advance precision immunotherapy. Herein, we review the biological mechanisms underlying the unconventional response patterns associated with ICB, describe strategies for the objective assessments of such responses, and also highlight the ongoing efforts to identify biomarkers, in order to guide treatment with ICB. We provide state-of-the-art knowledge of immune-related response evaluations, identify unmet needs requiring further investigations, and propose future directions to maximize the benefits of ICB therapy.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/67/1059/2325 / 631/67/1059/2326 / 631/67/1857 / 692/308/2779/109 / Antibodies, Monoclonal - therapeutic use / B7-H1 Antigen - antagonists & inhibitors / Biomarkers / Biomarkers, Tumor - genetics / Biomarkers, Tumor - metabolism / Cancer / Cancer immunotherapy / Cancer research / Cancer treatment / Clinical Trials as Topic / CTLA-4 Antigen - antagonists & inhibitors / CTLA-4 protein / Disease Progression / Enzyme regulation / Health aspects / Humans / Immune checkpoint / Immunotherapy / Immunotherapy - methods / Innovations / Medicine & Public Health / Monoclonal antibodies / Neoplasms - drug therapy / Neoplasms - genetics / Neoplasms - metabolism / Oncology / PD-1 protein / PD-L1 protein / Programmed Cell Death 1 Receptor - antagonists & inhibitors / review-article / Treatment Outcome / Tumors