Squamous cell carcinoma of the lung: improving the detection and management of immune-related adverse events

ABSTRACT

Introduction

Immune checkpoint inhibitors (ICIs) have revolutionized treatment for patients with non-small lung cancer (NSCLC). Currently approved ICIs are monoclonal antibodies that target programmed death receptor 1 (PD-1), its ligand PD-L1, or CTLA-4. With ICIs comes a novel collection of toxicities: immune-related adverse events (IRAEs). Management of IRAEs requires multidisciplinary expertise. We review the biology of IRAEs and their management in patients with squamous NSCLC.

Areas covered

We review the pathophysiology of ICIs and IRAEs. For IRAEs related to squamous NSCLC, Cochrane Central, EMBASE, and PubMed were queried for trials with patients with squamous cell carcinoma or adenocarcinoma histology, who were assessed for incidence rates of IRAEs. Thirteen trials met inclusion criteria. National guidelines are reviewed to outline management strategies for IRAEs.

Expert opinion

IRAEs are unique compared to standard chemotherapy. As the role of ICIs expand across all stages of squamous cell NSCLC and with different combinations of antineoplastics, management of IRAEs will become crucial. Optimal management of IRAEs requires multidisciplinary teamwork. Further investigation into the pathophysiology of IRAEs can enhance current management strategies.

KEYWORDS:

• CTLA-4
• immune checkpoint inhibitors
• immune-related adverse effects
• non-small cell lung cancer
• PD-1
• PD-L1
• squamous cell lung cancer

Declaration of interest

J Subramanian has served as a speaker for Astra-Zeneca, Boehringer-Ingelheim, G1 therapeutics, Jazz Pharma, Janssen, and has served as an advisor for Advisor - Astra-Zeneca, Boehringer-Ingelheim, Cardinal Health, Eli Lilly, G1 therapeutics, Jazz Pharma, Janssen. Novartis, Pfizer, Sanofi, Takeda. 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.

Review disclosure

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

Article highlights

• ICIs are essential in the treatment of squamous cell lung cancer, and their use is expanding from patients with advanced cancer to those with earlier stages of disease.

• ICIs are monoclonal antibodies that increase T cell activation through a variety of mechanisms.

• The pathophysiology of IRAEs is poorly understood, and may be dose-dependent, time-dependent, and/or agent-dependent.

• For squamous cell lung cancers, the most common adverse events experienced by patients on monotherapy with ICIs include asthenia, decreased appetite, dermatologic toxicity, diarrhea, fatigue, nausea, and pyrexia.

• The most common adverse events experienced by patients on ICIs in combination with chemotherapy include alopecia, anemia, nausea, neutropenia, and thrombocytopenia.

• Several national and international guidelines are available for the management of IRAEs, and grading is performed using the Common Terminology Criteria for Adverse Events (CTCAE).

• Low-grade IRAEs can be managed with close clinical surveillance and temporary interruption of ICI therapy.

• High-grade IRAEs require corticosteroids and in severe cases, permanent discontinuation of the ICI.

Additional information

Funding

The authors have no funding to report.