Treatment options after first-line immunotherapy in metastatic NSCLC

ABSTRACT

Introduction: The recent approvals of checkpoint inhibitors as single agents or in combination with chemotherapy with programmed death ligand 1 expression of < or ≥1% have challenged clinicians when it is time to begin a metastatic lung cancer patient in second-line therapy. The advantages given by immunotherapy over conventional chemotherapy such as improved overall survival and a better toxicity profile make the second-line clinical scenario more difficult for a patient who faces a likely inferior regimen as well as toxicity which may significantly impact the quality of life.

Areas covered: Options given today by the National Comprehensive Cancer Network are very limited, and essentially, we go back to conventional cytotoxic agents alone or in combination with biological agents if possible. In this article, we discuss the actual treatment available for this difficult scenario and some of the ongoing trials which aim to address this dilemma.

Expert commentary: This is an unmet need in lung cancer management; we need a better understanding of the mechanism of resistance to immunotherapy so we can target them once the patient moves to second-line treatment.

KEYWORDS:

• Checkpoint inhibition
• second line
• non-small cell lung cancer
• immunotherapy resistance
• mechanism of resistance

Article Highlights

• Immunotherapy alone or combo chemo/IO has become the cornerstone of treatment for NSCLC patients whose tumors do not harbor a driver mutation.

• Failure to frontline IO is a major issue today in thoracic oncology as second line for these patients consist mainly of systemic cytotoxic agents either as monotherapy or in combination with other biological agents.

• It is crucial that we understand the mechanisms of resistance to IO used in the frontline so we can target them in specific areas of the immune cycle.

• Several clinical trials look promising by combining IO with other agents who stimulate the cellular immune system.

• PARP inhibitors and multi-tyrosine kinase inhibitors are examples of agents being added upfront to regimen such as Keynote-189 to enhance the tumor response attained in the past with this regimen and delay resistance to it.

Declaration of Interest

Edgardo S Santos has received speaker fees from Genentech, Merck, Pfizer, Celgene, Takeda, Amgen, Dova, Novartis, Boehringer-Ingelheim, Sanofigenzyme, and Astrazeneca. 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 apart from those disclosed.

Reviewer Disclosures

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

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This paper received no funding.