Immunotherapy-chemotherapy combinations for non-small cell lung cancer: current trends and future perspectives

ABSTRACT

Introduction

In recent years, immunotherapy has become a pillar in the treatment of advanced, non-oncogene-addicted non-small cell lung cancer (NSCLC). Programmed death ligand 1 (PD-L1) expression is currently the only factor used to predict response to immunotherapy in clinical practice. Specifically, single-agent pembrolizumab as first-line therapy is approved for tumors with high expression of PD-L1 (≥50%) while immunotherapy and chemotherapy are approved for any PD-L1. However, combinations of immune-checkpoint inhibitors (ICIs) and other agents may confer higher benefit than immunotherapy alone in some circumstances.

Areas covered

We reviewed the available data regarding the combined use of ICIs and chemotherapy in patients with advanced, treatment-naïve NSCLC. In light of the benefit demonstrated in advanced disease, these combinations have been subsequently tested in other settings. We collected the most relevant findings regarding efficacy and safety of chemo-immunotherapy combinations in early and locally advanced NSCLC.

Expert opinion

Immune-chemotherapy combinations demonstrated benefit in the advanced setting, and this strategy in now being applied in the early and local advanced settings. A description of clinical and biological predictors of response is required in order to identify patients who may benefit the most from combination therapy.

KEYWORDS:

• anti-PD1
• anti-PD-L1
• anti-CTLA4
• immunotherapy
• immunotherapy-chemotherapy combination
• immune-checkpoint inhibitors
• lung cancer
• NSCLC

Article highlights

• The addition of anti PD-1 and anti PD-L1 agents to platinum doublet backbone has improved survival and response outcomes in advanced NSCLC in recent years.

• The dual blockade of anti CTLA-4 and anti PD-1 can spare some chemotherapy toxicity and carries a different safety profile which includes more immune-mediated reactions.

• Currently, there are no clinical or biological criteria to distinguish patients who should receive platinum-based chemotherapy plus anti PD-1 from those who should be treated with ‘short course’ chemotherapy with double immune checkpoint blockade.

• Novel combinations of immunotherapy and chemotherapy have been tested or are currently under study in both advanced and local or locally advanced stages.

• Finding new predictive biomarkers of response and toxicity is imperative as combinations strategies are gradually moving into neoadjuvant and adjuvant settings.

Acknowledgments

The authors wish to thank the following institutions for research grants supporting our studies involving immunotherapy in non-small cell lung cancer: 1) Italian Ministry of Health (5x1000 funds; CO-2016-02361470; Ricerca Corrente 2022-2024); 2) Bristol-Myers-Squibb (BMS 209-828). We are also grateful for the “Corrado Toscano” donation that supports S Marconi’s scholarship.

Declaration of interests

G Rossi acknowledges support from Roche, Novarits, Amgen, Merck Sharp & Dohme and Janssen. C Dellepiane acknowledges support from AstraZeneca, Bristol-Myers Squibb, Roche and Merck Sharp & Dohme. E Bennicelli acknowledges support from Bristol-Myers Squibb. G Barletta acknowledges support from AstraZeneca, Roche, Boehringer Ingelheim, Laboratoires Pierre Fabre and Bristol-Myers Squibb. M Tagliamento acknowledges support from Roche, Bristol-Myers Squibb, AstraZeneca, Takeda, Eli Lilly, Novartis and Amgen. C Genova acknowledges support from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Roche, Eli Lilly, Merck Sharp & Dohme, Sanofi, Takeda, Thermo Fisher, Amgen and Novartis, and has received grants from the Italian Ministry of Health. 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.

Additional information

Funding

This paper was not funded.