The role of immune checkpoint inhibitors in advanced non-small cell lung cancer

ABSTRACT

Introduction: Cancer immunotherapy represents a major therapeutic breakthrough. Immune checkpoint inhibitors alone or in the context of a combination are considered the new standard of care in advanced non-small cell lung cancer (NSCLC).

Areas covered: This review explains the biologic rationale behind the implementation of immune checkpoint inhibitors for the therapy of advanced NSCLC. It provides a detailed description of the clinical trials that have studied the various agents now in use and the results that lead to the currently approved indications. It also explores the area of established and developing biomarkers, and the trends of combining immunotherapy with other treatment modalities (chemotherapy, antiangiogenic agents, radiotherapy), or with other immune modulators.

Expert opinion: Immune checkpoint inhibitors have been established as the new standard of care for patients with advanced NSCLC. They can be administered according to PD-L1 expression upfront as monotherapy or in combination with chemotherapy– regardless of PD-L1 status – or in the later lines of therapy. They also represent a less toxic and more effective treatment choice than chemotherapy alone. The development of reliable biomarkers for patient selection and the subsequent use of the appropriate immune-based approach for each patient will define the role of immunotherapy in the years to come.

KEYWORDS:

• Immune checkpoint inhibitors
• advanced NSCLC
• nivolumab
• pembrolizumab

Article Highlights

• Immune checkpoint inhibitors are novel immunotherapy agents that regulate antitumor immune response, reinstating endogenous antitumor immunity.

• Their use in advanced NSCLC as monotherapy has resulted in durable responses and significant survival gains in 20–25% of patients.

• PD-L1 expression on tumor and immune cells is the only validated predictive biomarker, and there is a proportional benefit related to its expression. Other biomarkers are also been developed, like tumor mutation burden and immune gene signatures.

• Patients with tumors expressing PD-L1 >50% derive significant benefit from monotherapy with immune checkpoint inhibitors and should be offered this option in the first line of therapy.

• By combining immune checkpoint inhibitors with other treatment modalities (chemotherapy, other checkpoint inhibitors, antiangiogenic agents), observed responses and survival rates increased significantly, regardless of PD-L1 expression.

• The combination of chemotherapy and immune checkpoint inhibitors is now considered a standard care for patients with tumors expressing <50% PD-L1

• As it considers inoperable stage III NSCLC, administration of immunotherapy after the completion of definitive chemoradiotherapy is considered the new standard of care.

• Treatment sequencing, developing rational combinations and optimization of patient selection represent the major challenges of the future.

Acknowledgments

The authors would like to thank the scientific secretary Mrs. Vasso Athanasaki, for her attentive editing of this manuscript.

Declaration of interest

The authors have no 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.

Reviewers Disclosure

A reviewer on this manuscript has disclosed honoraria from Astra-zeneca, BMS, Roche, MSD. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Author Contribution

All authorss have contributed significantly to conception, design and execution of the study.

All authors have participated in drafting, reviewing, and/or revising the manuscript, and have approved its submission.

Additional information

Funding

This paper was not funded.