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Time since start of first-line therapy as a predictive clinical marker for nintedanib in patients with previously treated non-small cell lung cancer
- Source :
- Gaschler-Markefski, B, Sikken, P, Heymach, J V, Gottfried, M, Mellemgaard, A, Novello, S, Gann, C-N, Barrueco, J, Reck, M, Hanna, N H & Kaiser, R 2017, ' Time since start of first-line therapy as a predictive clinical marker for nintedanib in patients with previously treated non-small cell lung cancer ', E S M O Open, vol. 2, no. 1, e000102 . https://doi.org/10.1136/esmoopen-2016-000102, ESMO Open
- Publication Year :
- 2017
-
Abstract
- INTRODUCTION: No predictive clinical or genetic markers have been identified or validated for antiangiogenic agents in lung cancer. We aimed to identify a predictive clinical marker of benefit for nintedanib, an angiokinase inhibitor, using data from two large second-line non-small cell lung cancer Phase III trials (LUME-Lung 1 ([LL1] and LUME-Lung 2).METHODS: Predictive marker identification was conducted in a multi-step process using data from both trials; a hypothesis was generated, confirmed and validated. Statistical analyses included a stepwise selection approach, a recursive partitioning method and the evaluation of HRs, including treatment-by-covariate interactions. The marker was finally validated using a prospectively defined hierarchical testing procedure and treatment-by-covariate interaction for overall survival (OS) based on LL1.RESULTS: Time since start of first-line therapy (TSFLT) was identified as the only predictive clinical marker. A cut-off of 9 months was chosen for further analysis, based on HRs and recursive partitioning. The prospectively defined final validation using OS data from LL1 established the strong relationship between TSFLT and treatment with nintedanib. Patients with adenocarcinoma with TSFLT 9 months group (median OS 17.0 vs 15.1 months, HR 0.89 [95% CI 0.66-1.19]).CONCLUSIONS: Patients with shorter TSFLT derive a greater progression-free survival and OS benefit from nintedanib. This clinical marker could be used for patient selection and further investigation is warranted regarding pathways promoting aggressive tumour growth and antiangiogenic tyrosine kinase inhibitor benefit.
- Subjects :
- 0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
medicine.drug_class
Nintedanib
Recursive partitioning
Adenocarcinoma
Tyrosine-kinase inhibitor
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Non-small cell lung cancer
Internal medicine
medicine
Time since first-line treatment
Lung cancer
Original Research
Predictive marker
business.industry
Clinical marker
Stepwise regression
medicine.disease
3. Good health
Surgery
030104 developmental biology
chemistry
Genetic marker
030220 oncology & carcinogenesis
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Gaschler-Markefski, B, Sikken, P, Heymach, J V, Gottfried, M, Mellemgaard, A, Novello, S, Gann, C-N, Barrueco, J, Reck, M, Hanna, N H & Kaiser, R 2017, ' Time since start of first-line therapy as a predictive clinical marker for nintedanib in patients with previously treated non-small cell lung cancer ', E S M O Open, vol. 2, no. 1, e000102 . https://doi.org/10.1136/esmoopen-2016-000102, ESMO Open
- Accession number :
- edsair.doi.dedup.....53bf9381dc3b4bba3f15bccc1002fcfa