The role of checkpoint inhibitors immunotherapy in advanced non-small cell lung cancer in the elderly

ABSTRACT

Introduction: Immune checkpoint inhibition is a novel treatment modality that has brought a new hope to patients with advanced NSCLC. Several molecules targeting cytotoxic T-lymphocyte antigen 4 (CTLA4) or programmed cell death 1 receptor/programmed death ligand-1 (PD1/PD-L1) pathways are under evaluation in NSCLC and three of them are currently approved: nivolumab and atezolizumab for advanced NSCLC after prior chemotherapy and pembrolizumab for advanced NSCLC expressing PD-L1 ≥ 1% after at least one prior chemotherapy regimen and > 50% as a first-line response.

Areas covered: To date, the efficacy and toxicity of immune checkpoint inhibitors in the elderly is unclear because available studies involved mainly a low number of elderly patients. In this paper, the authors discuss the frailty of the elderly patient and the challenges of choosing the best therapeutic strategy, focusing on the role of immune checkpoint inhibitors.

Expert opinion: There are several outstanding goals that need to be met for the proper and safe use of immunotherapeutic drugs. In terms of the elderly, it is true that age-tailored clinical trials are needed to confirm the real impact of immunotherapy and harmonize the standard of care in this specific demographic.

KEYWORDS:

• Anti-PD1
• Anti-PD-L1
• Atezolizumab
• Checkpoint inhibitors
• Elderly
• Immunosenescence
• Immunotherapy
• Nivolumab
• non-small cell lung cancer
• Pembrolizumab

Article highlights

• Immune checkpoint inhibition is a novel treatment modality that has brought a new hope to patients with advanced NSCLC;

• No randomized phase III trials on efficacy of PD1/PD-L1 targeting agents in the elderly lung patients with advanced NSCLC are available: it remains difficult to confirm the impact of the immunotherapy in elderly;

• The ‘immunosenescence phenomenon’ and how it could affect the efficacy and/or the toxicity of immune checkpoint inhibitors is unclear;

• As second-line, a consistent treatment effect favoring nivolumab was observed in most prespecified subgroups, except in the group of NSCLC patients ≥ 75 years, possibly due to statistical reasons;

• Pembrolizumab demonstrated improved overall survival in previously treated NSCLC patients aged ≥ 75 years;

• Checkpoint inhibitors reported an improved safety profile compared to traditional chemotherapeutic agents or molecularly targeted therapies. However, little is known about the safety of these agents in elderly patient population.

This box summarizes key points contained in the article.

Declaration of interest

C Gridelli is on the speaker’s bureau and is an advisory board member for Bristol-Myers Squibb, Merck Sharp and Dohme, Pfizer Inc., Roche, Novartis, AstraZeneca, Eli Lilly and Company and Celgene. 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 manuscript has not been funded.