Experience with targeted next generation sequencing for the care of lung cancer: Insights into promises and limitations of genomic oncology in day-to-day practice

Abstract

Introduction Tumor genotyping using single gene assays (SGAs) is standard practice in advanced non-small-cell lung cancer (NSCLC). We evaluated how the introduction of next generation sequencing (NGS) into day-to-day clinical practice altered therapeutic decision-making. Methods Clinicopathologic data, tumor genotype, and clinical decisions were retrospectively compiled over 6 months following introduction of NGS assay use at our institution in 82 patient-tumor samples (7 by primary NGS, 22 by sequential SGAs followed by NGS, and 53 by SGAs). Results SGAs identified abnormalities in 34 samples, and all patients with advanced EGFR-mutated or ALK-rearranged tumors received approved tyrosine kinase inhibitors (TKIs) or were consented for clinical trials. NGS was more commonly requested for EGFR, ALK, and KRAS-negative tumors (p<0.0001). NGS was successful in 24/29 (82.7%) tumors. Of 17 adenocarcinomas (ACs), 11 (7 from patients with ≤15 pack-years of smoking) had abnormalities in a known driver oncogene. This led to a change in decision-making in 8 patients, trial consideration in 6, and off-label TKI use in 2. Of 7 squamous cell (SC) carcinomas, 1 had a driver aberration (FGFR1); 6 had other genomic events (all with TP53 mutations). In no cases were clinical decisions altered (p=0.0538 when compared to ACs). Conclusions Targeted NGS can identify a significant number of therapeutically-relevant driver events in lung ACs; particularly in never or light smokers. For SC lung cancers, NGS is less likely to alter current practice. Further research into the cost effectiveness and optimal use of NGS and improved provider training in genomic oncology are warranted.

Next-Generation Sequencing Approach to Non–Small Cell Lung Carcinoma Yields More Actionable Alterations

“…These observations support the idea to expand the NGS testing beyond adenocarcinoma and to include other histologic subtypes such as SCC and even LCNEC, particularly for patients with unusual clinical characteristics such as rapid course of progression, younger age, and no history of tobacco smoking. This is in contrast to the study by Ranganchari et al 23 that showed only 1 driver mutation in SCC (FGFR1), information that did not change the clinical treatment decision. Therefore, the authors concluded that NGS testing in SCC is less likely to alter current practice.…”

Pulse Afatinib for ERBB2 Exon 20 Insertion–Mutated Lung Adenocarcinomas

“…Patient-tumor pairs followed at Beth Israel Deaconess Medical Center (BIDMC) with a diagnosis of lung adenocarcinoma were identified through an ongoing Institutional Review Board-approved study [12]. Pathologic data, tumor genotype, toxicity to afatinib and radiographic parameters were gathered from retrospective chart extraction.…”

De novo ALK kinase domain mutations are uncommon in kinase inhibitor-naïve ALK rearranged lung cancers

“…Patient-tumor pairs followed at the Thoracic Oncology multidisciplinary clinic at Beth Israel Deaconess Medical Center (BIDMC) with a diagnosis of NSCLC were registered through an ongoing Institutional Review Board-approved study [17–19]. Pathologic data, tumor genotype and radiographic images were assembled from retrospective chart extraction.…”

“…RNA was isolated from tumor tissue for evaluation of fusion partners using PCR-based or next generation sequencing assays, while DNA was isolated to sequence exons corresponding to the kinase domain of ALK (exons 21 to 27), as previously reported [16, 17, 20, 21]. …”