The predictive value of the microbiome (throat swabs, stool and of bronchial samples) to identify patients who will relapse during durvalumab treatment after CRT (False negative Rate) at 6 months. Exploratory endpoints include the effects of antibiotic therapy before and during IO treatment on toxicity and response rate. The role of exhaled breath analysis in prediction of response and toxicity will also be investigated.
In this observational study we aim to investigate the predictive value of the microbiome (throat swabs and stool) to identify patients who will relapse during durvalumab treatment after CRT (False negative Rate) at 6 months. Collection of stool and throat swipe before start of durvalumab treatment; sampling of blood and exhaled air for analysis of volatile organic compounds. Improved clinical outcomes after adjuvant treatment with durvalumab following concurrent chemoradiotherapy (CCRT) for locally advanced NSCLC (PACIFIC trial), led to the rapid adoption of this treatment strategy as standard of care. However, despite the improved progression free survival and overall survival, recurrence rate remains high. Approximately 45% of patients will relapse within 1 year, despite adjuvant durvalumab therapy. To date no performant biomarker predicting treatment response or failure nor toxicity exists and the number of prospective studies addressing this issue is limited. Both PD-L1 TPS and TMB should be considered 'enriching' parameters improving response-chances, but they are far from an ideal biomarker. Non-invasive biomarkers are essential in the future for better patient selection and therapy allocation. One of the potential non-invasive biomarkers of interest is the microbiome.
Study Type
OBSERVATIONAL
Enrollment
126
Kristof Cuppens
Hasselt, Flanders, Belgium
Piet Verkouteren
Aalst, Belgium
Ingel Demedts
Roeselare, Belgium
Lynn Decoster
Turnhout, Belgium
Prediction of outcome (progression) based on microbiome analysis
To investigate the predictive value of the microbiome (throat swabs and stool) to identify patients who will relapse during durvalumab treatment after CRT (False negative Rate) at 6 months
Time frame: 1 year
Prediction of toxicity based on microbiome analysis
To investigate the predictive value of the microbiome (throat swabs and stool ) to identify patients that develop irAE's during durvalumab treatment after CRT.
Time frame: 1 year
Prediction of outcome (disease controle rate) based on microbiome analysis
To determine disease control rate (DCR ie. Stable disease, partial response, and complete response) and PFS at 6 months and correlate to the microbiome.
Time frame: 1 year
Relationship between circulating immune cells and microbiome outcome
To investigate to what extend cytological characteristics of circulating immune cells obtained from responders and non-responders differ and to explore to what extend these differences relate to the microbiome.
Time frame: 1 year
Value of analysis of exhaled breath at 6 months
To investigate the predictive value of exhaled breath analysis (by eNose) to identify patients who will relapse or progress during durvalumab treatment after CRT (False negative Rate) at 6 months.
Time frame: 6 months
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Netherlands Cancer Institute
Amsterdam, Netherlands
Leiden University Medical center
Leiden, Netherlands