Actionable Molecular Alterations Are Revealed in Majority of Advanced Non-Small Cell Lung Cancer Patients by Genomic Tumor Profiling at Progression after First Line Treatment

Abstract

Background: Genomic profiling in advanced Non-Small Cell Lung cancer (NSCLC) can reveal Actionable Molecular Alterations (AMAs). Our study aims to investigate clinical relevance of re-biopsy after first line treatment, by reporting on acquired and persistent AMAs and potential targeted treatments in a real-time cohort of NSCLC patients. Methods: Patients with advanced NSCLC receiving first-line treatment were prospectively included in an observational study (NCT03512847). Genomic profiling was performed by TruSight Oncology 500 HT gene panel on tumor tissue collected at diagnosis and at time of progression. Results: The 92 patients re-biopsied at progression had received immunotherapy (n = 44), chemotherapy (n = 44), or combination treatment (n = 4). In 87 of these patients (95%), successful genomic profiling was performed at both the diagnostic biopsy and the re-biopsy. In 74 patients (85%), ≥1 AMA were found. The AMAs were acquired in 28%. The most frequent AMAs were observed in TP53 (45%), KRAS (24%), PIK3CA (6%), and FGFR1 (6%). Only five patients (5%) received targeted treatment mainly due to deterioration in performance status. Conclusions: Re-biopsy at progression revealed acquired AMAs in approximately one third of patients, and 85% had at least one AMA with the potential of receiving targeted treatment, thus strengthening the clinical relevance of re-biopsy.

Circulating Tumor DNA Monitoring Reveals Molecular Progression before Radiologic Progression in a Real-life Cohort of Patients with Advanced Non–small Cell Lung Cancer

“…Exclusion criteria were: Other active cancers and contraindications for systemic treatment. The study cohort has previously been described in two publications, reporting on feasibility of rebiopsy including programmed death-ligand 1 (PD-L1) changes ( 31 ) and actionable molecular alterations ( 32 ).…”

“…Descriptions of DNA extraction, sequencing, and interpretation are available in ref. 32 . Sequencing data including likely pathogenic and pathogenic somatic mutations including nonsense, frameshift, missense, and splice site alterations in cancer-related genes, are available in Supplementary Table S1 , which also details location of biopsies, microsatellite instability, and tumor mutational burden.…”