Current data on predictive markers for anti-angiogenic therapy in thoracic tumours

Our plain-English summary of Current data on predictive markers for anti-angiogenic therapy in thoracic tumours, by N. Reinmuth, M. Thomas, M. Meister, et al (The European Respiratory Journal, 2010).

The study

• Authors: N. Reinmuth, M. Thomas, M. Meister, P.A. Schnabel, M. Kreuter
• Journal: The European Respiratory Journal
• Published: 2010;36(4):915-24
• Type of article: Review
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The fact that growth and spread of tumours are dependent on angiogenesis has led to the investigation of the role of anti-angiogenic agents in the therapeutic strategies for thoracic tumours such as nonsmall cell lung cancer or mesotheliomas. Since various angiogenic factors may contribute to the regulation of angiogenesis in the individual tumour, in the era of increasing amounts of clinically tested agents it is of utmost importance to properly select patients that may benefit from a specific therapy. Due to the complex nature of tumour angiogenesis, various biomarkers may be applicable. For example, the profile of activated angiogenic pathways in endothelial cells may be determined in order to make conclusions about the relevance of inhibiting a given pathway by a selected agent. Moreover, changes in protein expression in stromal and tumour cells, as well as structural alterations in the vasculature, may be used for predicting and monitoring the clinical effects of such a therapy. In this review, the current data from clinical studies evaluating predictive markers for anti-angiogenic agents in thoracic cancers are summarised. Besides giving clinical examples, the rationales for investigating various parameters based on pre-clinical studies are described.

In plain English

This article was a review. The authors summarised published clinical and laboratory research on markers that might predict which patients with chest cancers, mainly non-small cell lung cancer and malignant mesothelioma, benefit from drugs that block tumour blood-vessel growth (anti-angiogenic drugs such as bevacizumab). The article did not discuss asbestos. One reviewed trial gave 108 mesothelioma patients cisplatin and gemcitabine with or without bevacizumab. Among those who received bevacizumab, baseline blood levels of the growth factor VEGF at or below the median were linked to significantly better progression-free and overall survival. The authors wrote that this may suggest some mesothelioma patients could benefit, but that confirmatory studies are needed. In a large lung cancer trial, low baseline levels of an adhesion molecule (ICAM) predicted better progression-free survival, but not overall survival, when bevacizumab was added. The authors noted that measurement methods were not standardised and that biomarker tests often covered only a small share of trial patients. They wrote that the search for biomarkers had just begun.

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 of clinical and preclinical studies on predictive markers for anti-angiogenic therapy; no search method is described
• Who was studied: Published clinical studies (supported by preclinical studies) in patients with thoracic tumours, mainly non-small cell lung cancer and malignant mesothelioma
• Exposure: Not an asbestos exposure study. The treatments reviewed were anti-angiogenic drugs (for example bevacizumab, vandetanib, sorafenib), assessed with tissue and blood markers.
• Main results:
  • Reviewed phase II trial in 108 mesothelioma patients (cisplatin and gemcitabine with or without bevacizumab): among patients who received bevacizumab, baseline VEGF levels at or below the median were associated with significantly improved progression-free survival (p = 0.043) and overall survival (p = 0.028)
  • In the same mesothelioma trial, higher baseline plasma VEGF levels were associated with shorter progression-free and overall survival
  • A reviewed phase II study treated 51 malignant mesothelioma patients with sorafenib. The marker results from that study had not been reported.
  • ECOG4599 lung cancer trial: low baseline ICAM levels were a significant predictive factor for improved progression-free survival (HR 2.14, 95% CI 1.31 to 3.48) but not overall survival (HR 1.39, 95% CI 0.84 to 2.3) when bevacizumab was added to chemotherapy
  • ECOG4599: patients with high pre-treatment VEGF levels were more likely to respond to bevacizumab-containing therapy, but VEGF level was not predictive of survival
  • The authors knew of no clinical study of how anti-angiogenic therapy affects microvessel density in non-small cell lung cancer
• The authors' conclusion: The authors concluded that the search for biomarkers has just begun, and that a combination of markers is likely to be more useful than any single factor. For mesothelioma, they wrote that the bevacizumab results may suggest benefit for some patients but need confirmation.
• Limitations the authors state:
  • Biomarker measurement technology has not been standardised
  • In most clinical studies, biomarker testing covered only a small percentage of the patients enrolled, which questions how representative the findings are
  • In ECOG4599, VEGF measurements were available for only 166 of 878 patients
  • A biopsy taken before first treatment may not reflect the tumour's biology at later treatments

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: Angiogenesis, Lung Cancer, Mesothelioma, Biomarker.

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• ¹⁸F-FDG uptake on PET could be a predictive marker of excision repair cross-complementation group 1 (ERCC1) expression in patients with thoracic neoplasms? — K. Kaira, M. Endo, et al. (2012)

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