Genetic evolution to tyrosine kinase inhibitory therapy in patients with EGFR-mutated non-small-cell lung cancer.

Autor: Martinez-Marti A; Department of Medical Oncology, Vall d'Hebron University Hospital (VHUH), Barcelona, Spain.; Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.; Autonomous University of Barcelona (UAB), Barcelona, Spain., Felip E; Department of Medical Oncology, Vall d'Hebron University Hospital (VHUH), Barcelona, Spain.; Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.; University of Vic (UVIC) Central University of Catalonia (UCC), Barcelona, Spain., Mancuso FM; Cancer Genomics Group, VHIO, Barcelona, Spain., Caratú G; Cancer Genomics Group, VHIO, Barcelona, Spain., Matito J; Cancer Genomics Group, VHIO, Barcelona, Spain., Nuciforo P; Molecular Oncology Group, VHIO, Barcelona, Spain., Sansano I; Pathology Department, VHUH, Barcelona, Spain., Diaz-Mejia N; Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain., Cedrés S; Department of Medical Oncology, Vall d'Hebron University Hospital (VHUH), Barcelona, Spain.; Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain., Callejo A; Department of Medical Oncology, Vall d'Hebron University Hospital (VHUH), Barcelona, Spain.; Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain., Iranzo P; Department of Medical Oncology, Vall d'Hebron University Hospital (VHUH), Barcelona, Spain.; Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain., Pardo N; Department of Medical Oncology, Vall d'Hebron University Hospital (VHUH), Barcelona, Spain.; Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain., Miquel JM; Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain., Navarro A; Department of Medical Oncology, Vall d'Hebron University Hospital (VHUH), Barcelona, Spain.; Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain., Vivancos A; Cancer Genomics Group, VHIO, Barcelona, Spain., Sansó M; Cancer Genomics Group, VHIO, Barcelona, Spain. miriam.sanso@ssib.es.; Balearic Islands Health Research Institute (IdISBa), Palma de Mallorca, Spain. miriam.sanso@ssib.es.; Genomics for Precision Oncology Group, Health Research Institute of the Balearic Islands (IdISBa), University Hospital Son Espases (HUSE), Palma de Mallorca, Spain. miriam.sanso@ssib.es.
Jazyk: angličtina
Zdroj: British journal of cancer [Br J Cancer] 2021 Nov; Vol. 125 (11), pp. 1561-1569. Date of Electronic Publication: 2021 Oct 01.
DOI: 10.1038/s41416-021-01558-9
Abstrakt: Background: Tumour heterogeneity impacts the efficacy of metastatic cancer treatment even if actionable mutations are identified. Clinicians need to understand if assessing one lesion provides reliable information to drive a therapeutic decision in non-small-cell lung cancer (NSCLC) patients.
Methods: We analysed inter-tumour heterogeneity from five autopsied individuals with NSCLC-harbouring mutations in the epidermal growth factor receptor (EGFR), treated with EGFR tyrosine kinase inhibitors (TKIs). Through a comprehensive next-generation sequencing (NGS) oncopanel, and an EGFR panel for digital droplet PCR (ddPCR), we compared metastases within individuals, longitudinal biopsies from the same lesions and, whenever possible, the primary naive tumour.
Results: Analysis of 22 necropsies from five patients revealed homogeneity in pathogenic mutations and TKI-resistance mechanisms within each patient in four of them. In-depth analysis by whole-exome sequencing from patient 1 confirmed homogeneity in clonal mutations, but heterogeneity in passenger subclonal alterations. Different resistance mechanisms were detected depending on the patient and line of treatment. Three patients treated with a c-MET inhibitor in combination with TKI lost MET amplification upon progression.
Conclusion: At a given point and under selective TKI pressure, a single metastasis biopsy in disseminated tumours from EGFR-mutated NSCLC patients could provide a reasonable assessment of actionable alterations useful for therapeutic decisions.
(© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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