Promising predictors of checkpoint inhibitor response in NSCLC

ABSTRACT

Introduction

The development of immune-checkpoint inhibitors targeting the programmed death-1 (PD-1) and its ligand (PD-L1) axis has transformed the treatment paradigm in non-small-cell lung cancer, bringing about unprecedented 5-year survival rates. Despite this dramatic improvement, roughly 70% of patients do not derive durable benefit from these treatments, illustrating the need for predictive biomarkers.

Areas covered

In this review, we will discuss what makes a successful biomarker and analyze the role and significance of currently available options, including PD-L1, oncogenic alterations and tumor mutation burden. We then discuss potential biomarkers on the horizon, including the microbiome, tumor infiltrating lymphocytes, neutrophil-to-lymphocyte ratio, gene signatures and the emerging field of multiomics.

Expert opinion

To date, only PD-L1 is clinically validated as a positive predictor of response to immunotherapy, yet the need to refine patient selection has never been stronger, given the indication for checkpoint inhibitors alone or in combination in all non-oncogene driven non-small-cell lung cancer patients receiving front-line therapy. Prospective validation of the above-mentioned potential biomarkers, either alone or in combination, may help to elaborate improved predictive tools.

KEYWORDS:

• NSCLC
• biomarkers
• immunotherapy
• checkpoint-inhibition
• TMB

Article highlights

• PD-L1 remains the strongest predictor of response to immune-checkpoint inhibitors in non-small-cell lung cancer.

• Conversely, oncogenic alterations such as EGFR and ALK appear to predict a lack of response.

• The potential role of tumour mutation burden remains unclear, but it is not appropriate for patient selection today.

• Promising biomarkers are on the horizon, either as single tests or in combination, but require prospective validation.

Declaration of interest

A. Addeohas received compensation from Bristol-Myers Squibb, AstraZeneca, Merck Sharpe & Dohme, Takeda, Pfizer, Roche and Boehringer Ingelheim for participating on advisory boards.

A. Friedlaender has received compensation from Roche, Pfizer, Astellas and Bristol-Myers Squibb for service as a consultant. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded