The efficacy of immune checkpoint inhibitors in thoracic malignancies

Our plain-English summary of The efficacy of immune checkpoint inhibitors in thoracic malignancies, by J. Remon, F. Facchinetti, B. Besse (European Respiratory Review, 2021).

The study

• Authors: J. Remon, F. Facchinetti, B. Besse
• Journal: European Respiratory Review
• Published: 2021;30(162)
• Type of article: Review
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The advent of immune checkpoint inhibitors (ICIs) has rapidly transformed the treatment paradigm for multiple cancer types, including thoracic malignancies. In advanced non-small cell lung cancer (NSCLC), ICIs have shifted treatment paradigm and improved overall survival reaching almost one-third of patients alive at 5 years. ICIs therapies have also modified the therapeutic strategy in first-line setting in metastatic small-cell lung cancer (SCLC) patients as well as in malignant pleural mesothelioma (MPM) improving the overall survival compared with standard treatment. This phenomenon is of huge relevance as both SCLC and MPM were considered orphan diseases without any significant improvement in the therapeutic strategy in the first-line setting during the last 15 years. In this review, we aim to review the efficacy of ICI in thoracic malignancies either in monotherapy or in combination, according to predictive biomarkers, and to the US Food and Drug Administration and the European Medicines Agency approvals of treatment strategies. We address the efficacy of these agents, especially in NSCLC according to PD-L1 expression and histologic subtype.

Copyright ©The authors 2021.

In plain English

This article was a commissioned, peer-reviewed review, not an original study. The authors reviewed published trials of immune checkpoint inhibitor drugs, which block PD-1, PD-L1 or CTLA-4, in four groups of chest cancers: non-small cell lung cancer, small-cell lung cancer, malignant pleural mesothelioma and thymic epithelial tumours. Asbestos appeared only as background, as one reason mesothelioma was thought a candidate for these drugs. The review did not study asbestos exposure. The authors reported that in the CheckMate 743 trial in unresectable malignant pleural mesothelioma, first-line nivolumab plus ipilimumab improved overall survival compared with platinum-pemetrexed chemotherapy (hazard ratio 0.74, 95% CI 0.60–0.91), with 1- and 2-year survival of 60% and 40%. In that trial's subgroup analysis by histology, the authors described superiority of the combination in non-epithelioid mesothelioma only (hazard ratio 0.46, 95% CI 0.31–0.68). For epithelioid cases the hazard ratio was 0.86 (95% CI 0.69–1.08). The PROMISE trial of pembrolizumab versus chemotherapy in previously treated patients did not meet its endpoints. The authors concluded that these drugs had become standard care in both lung cancer types and would likely change care for non-epithelioid mesothelioma.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review (commissioned, peer reviewed) of published clinical trials and studies of immune checkpoint inhibitors
• Who was studied: No study population of its own. The review covered published trials in patients with non-small cell lung cancer, small-cell lung cancer, malignant pleural mesothelioma (MPM) and thymic epithelial tumours (TET).
• Exposure: Immune checkpoint inhibitor drugs (PD-1, PD-L1 and CTLA-4 inhibitors such as nivolumab, ipilimumab, pembrolizumab, atezolizumab, durvalumab, tremelimumab), alone or combined with chemotherapy. Asbestos exposure was mentioned only as background for mesothelioma and was not studied.
• Main results:
  • Reviewed trial (CheckMate 743), first-line treatment of unresectable MPM: nivolumab plus ipilimumab improved overall survival compared with chemotherapy in the intention-to-treat population, hazard ratio 0.74 (95% CI 0.60–0.91).
  • Reviewed trial (CheckMate 743): the intention-to-treat hazard ratio for overall survival was 0.74 (95% CI 0.60–0.91).
  • Reviewed trial (CheckMate 743): 1-year overall survival was 60% and 2-year overall survival was 40% with nivolumab plus ipilimumab.
  • Reviewed trial (CheckMate 743), subgroups by histology: the authors described superiority of nivolumab plus ipilimumab in non-epithelioid MPM only, hazard ratio 0.46 (95% CI 0.31–0.68). In epithelioid cases the hazard ratio was 0.86 (95% CI 0.69–1.08).
  • Reviewed trial (CheckMate 743): the authors attributed the large superiority in non-epithelioid cases to poor results with chemotherapy in those cases. Outcomes in the immunotherapy arm did not differ by histotype.
  • Reviewed trial (CheckMate 743): PD-L1 expression did not correlate with outcome. The hazard ratio for overall survival was 0.94 (95% CI 0.62–1.40) in PD-L1 below 1% and 0.69 (95% CI 0.55–0.87) in PD-L1 of 1% or more.
  • Reviewed trial (PROMISE), previously treated MPM: pembrolizumab versus chemotherapy did not achieve the progression-free survival primary endpoint or overall survival.
  • Reviewed trial (DETERMINE), MPM: CTLA-4 inhibition with tremelimumab did not show superiority over placebo.
  • Reviewed trial (KEYNOTE-024), non-small cell lung cancer with PD-L1 of 50% or more: 5-year overall survival was 32% with pembrolizumab and 16% with chemotherapy.
• The authors' conclusion: The authors concluded that immune checkpoint inhibitors had become standard of care in non-small cell and small-cell lung cancer, while their role in MPM and TET was still to be defined. In MPM, they concluded that recent evidence would likely change the standard of care for non-epithelioid disease, where double PD-1/CTLA-4 blockade performed far better than chemotherapy.
• Limitations the authors state:
  • The authors noted that too few non-epithelioid MPM cases were included in trials or retrospective series to draw conclusions about whether they respond better to immunotherapy.
  • The authors noted that PD-L1 is not a perfect predictive biomarker: some patients with high PD-L1 do not benefit, and some with PD-L1 negative tumours do.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: checkpoint inhibitors, Non-Small Cell Lung Cancer, Overall Survival, Lung Cancer, Pleural Mesothelioma, Biomarker, PD-L1, Histological Subtype.

Related studies

• Moving Immune Checkpoint Blockade in Thoracic Tumors beyond NSCLC — F. Facchinetti, A. Marabelle, et al. (2016)
• Potential of fluoropyrimidine to be an immunologically optimal partner of immune checkpoint inhibitors through inducing immunogenic cell death for thoracic malignancies — H. Kozai, H. Ogino, et al. (2024)
• Antibody drug conjugates in thoracic malignancies — J.M. Pacheco, D.R. Camidge (2018)
• Immune checkpoint inhibitors in non-small cell lung cancer (NSCLC): Approaches on special subgroups and unresolved burning questions — J. Remon, N. Vilariño, et al. (2018)
• Repositioning PARP inhibitors in the treatment of thoracic malignancies — F. Passiglia, M.L. Reale, et al. (2021)
• Photodynamic Therapy in Non-Gastrointestinal Thoracic Malignancies — B. Kidane, D. Hirpara, et al. (2016)

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