Releasing the brake: safety profile of immune check-point inhibitors in non-small cell lung cancer

ABSTRACT

Introduction: Immune check-point inhibitors are now employed as single-agents in current practice for the treatment of advanced non-small cell lung cancer (NSCLC), while combinations of different inhibitors are being evaluated in clinical trials. Although the safety profile of these compounds, with particular reference to drugs targeting programmed death protein 1 (PD-1) and its ligand (PD-L1), is generally considered manageable, peculiar, immune-related toxicities may onset.

Areas covered: This review focuses on the immune-related adverse events (irAEs) observed during immune check-point blockade in NSCLC and their management. The authors report the incidence of irAEs based on the currently available data involving NSCLC and provide recommendations on the general approach to irAEs, as well as indications for the most relevant site-specific events.

Expert opinion: Since irAEs may involve a wide range of organs and systems and are potentially reversible if promptly treated, early diagnosis should always be achieved; this might be particularly challenging when other potential causes of toxicity are suspected, such as infections or concurrent treatments. Finally, drugs active on the PD-1/PD-L1 axis appear to be generally manageable even when they are administered to patients with relevant comorbidities, provided that adequate clinical monitoring is performed.

KEYWORDS:

• Non-small cell lung cancer
• immune check-point inhibitor
• safety
• immune-related adverse events

Article highlights

• Cancer immunotherapy with immune check-point inhibitors is associated with impressive results in advanced non-small cell lung cancer, and has rapidly become a standard in the treatment of this malignancy.

• While the safety profile of immune check-point inhibitors is generally manageable, especially for PD-1 and PD-L1 inhibitors, specific immune-related adverse events may occur during treatment.

• Immune-related adverse events are caused by the blockade of physiological self-tolerance mechanisms exerted by immune check-point inhibitors, and might involve a wide range of organs and systems; relevant sites of toxicity include skin, liver, endocrine organs, gastrointestinal tract and lungs.

• Most immune-related toxicities are mild or moderate; however, serious or even life-threatening events have been reported. If promptly approached, most events can be controlled or resolved.

• Immunosuppression with corticosteroids represents the cornerstone of the management of immune-related adverse events, although refractory events might require further immunosuppressive agents; additionally, selected toxicities require specific measures, such as endocrinopathies requiring long-term hormonal replacement.

This box summarizes key points contained in the article.

Declaration of interest

C Genova and E Rijavec received honoraria from Bristol-Myers-Squibb and from Astra Zeneca; G Barletta received honoraria from Astra Zeneca; F Grossi received honoraria from Bristol-Myers-Squibb, Merck Sharp and Dome, Roche and Astra Zeneca. 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.

Additional information

Funding

This paper was not funded.