National clinical study

Early detection of treatment failure by circulating tumor DNA in advanced non-small cell lung cancer

The purpose of the study is early detection of treatment failure in patients with advanced non-small cell lung cancer (NSCLC) without targetable mutations to prevent ineffective treatment and needless toxicity. We are performing a prospective exploratory study in order to:

1) assess how the levels of circulating tumor DNA (ctDNA) during treatment correlate to treatment response.

2) concurrently perform comprehensive molecular profiling to identify resistance mechanisms and molecular therapeutically actionable targets for a more effective treatment strategy.

3) assess how specific ctDNA variants and total cfDNA is associated with immune-mediated antitumor response in immunotherapy-treated NSCLC patients.

The project received funding in 2020 

Abstract

Lung cancer is the leading cause of cancer related death. The introduction of new therapies in treatment of advanced non-small cell lung cancer during recent years, such as immunotherapy and targeted/personalized treatment has bettered the prognosis. Though the response rates are widely varying due to primary or acquired resistance. There is an urgent need of early detection of treatment failure and exploration of resistance mechanims to prevent long-lasting ineffective, costly treatments and to better treatment response through targeted treatment.

Purpose and Methods
In our research group a strong cross regional collaboration between Zealand University Hospital, Ålborg University Hospital, Vejle Hospital and Centre of Genomic Medicine, Rigshospitalet, has been established, enabling a high inclusion rate and high quality analyses and interpretation of results. In this prospective exploratory study, we aimed to assess how the levels of circulating tumor DNA (ctDNA), measured in plasma, during treatment correlate to treatment response. In addition we aimed to identify resistance mechanisms and molecular therapeutically actionable targets.

Results
All relevant approvals have been obtained and we have included 218 patients. Preliminary results are promising, showing correlation between the level of ctDNA and response to treatment, and also the ability to reveal new resistance mutations during treatment. An abstract covering the preliminary results have been presented at the European Respiratory Society (ERS) International Congress 2020.

Perspective
Based on the findings in this study, a national interventional study is planned to investigate the clinical utility and significance of liquid biopsy in monitoring treatment efficacy and treatment resistance in advanced NSCLC.

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