Repeat Molecular Profiling Detects Actionable Genetic Alterations in Patients with Progressive Lung Cancer

This study assessed the value of repeat genomic profiling on post-progression biopsies in patients with EGFR/ALK-positive stage IV non–small-cell lung cancer (NSCLC) treated with tyrosine kinase inhibitors (TKIs), with the intent of identifying resistance mutations, informing actionable targets, assessing clinical trial eligibility, and determining the costs of repeat biopsy.

Post-progression tumor biopsies from 32 eligible consenting patients with stage IV NSCLC and known EGFR/ALK aberrations at Princess Margaret Cancer Center underwent genomic profiling of hotspots, fusions, and copy number variations in 161 cancer-associated genes. Of the 32 patients, 27 (84%) completed testing and 5 (16%) failed testing due to insufficient tissue. The median age of the study cohort was 56 years; the majority were female (59%; n = 16), never-smokers (74%; n = 20), had Eastern Cooperative Oncology Group performance status 0 to 1 (81%; n = 22), and were Asian (67%; n = 18). Prior to re-biopsy, the majority had EGFR mutations (81%; n = 22) and 19% (n = 5) had ALK fusions. Patients had received a median of 1.3 prior lines of TKI therapy.

Overall, repeat genomic profiling identified 16 patients with resistance mechanisms, including 1 with small-cell transformation and associated TP53 and RB1 mutations, 3 patients with acquired EGFR C797S mutations, 3 with EGFR amplification, and 3 with acquired ALK resistance point mutations. Additional actionable targets were identified in 5 (19%) patients, which included MET exon 14 skip mutation (n = 1), MET amplification (n = 2), BRAF V600E (n = 1), and BRAF fusion (n = 1). Based on genomic profiling results, new clinical trial options were identified for the majority of patients (n = 18). Incremental costs for repeat genomic profiling were approximately $880 (Can$) per case.

The results of this study indicate that the majority of patients with progressing stage IV NSCLC and the development of resistance to targeted therapies benefited from repeat molecular profiling to detect actionable resistance mechanisms and facilitate clinical trial enrollment, supporting the routine use of repeat molecular profiling in clinical practice.

Source: Barron CC, et al. J Clin Oncol. 2021;39(suppl 15):Abstract 3126.

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