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D. Rangachari
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-027 - Targeted next Generation Sequencing in Lung Cancer: Genomic Oncology in Daily Practice (ID 103)
09:30 - 09:30 | Author(s): D. Rangachari
- Abstract
Background:
Tumor genotyping using single gene assays (SGAs) is a standard approach in the management of advanced NSCLC. We evaluated how therapeutic decision-making was altered by the introduction of next generation sequencing (NGS) into routine clinical practice.
Methods:
Clinicopathologic data, tumor genotype, and clinical decisions were retrospectively compiled over 6 months following introduction of NGS assay use at our institution.
Results:
82 tumors were genotyped: 75 by SGAs, 7 by NGS alone, and 22 by SGAs and NGS. SGAs identified 10 EGFR-mutated, 3 ALK-rearranged, and 21 KRAS-mutated tumors. Sequential testing with SGAs followed by NGS was more common for patients with EGFR/ALK/KRAS-negative tumors (22/29 or 75.9%) and adenocarcinomas (ACs) (21/22 or 95.5%). Most EGFR/ALK/KRAS-negative tumors were sent for NGS (21/35 or 60%). Of 17 ACs, 10 harbored abnormalities in a known driver oncogene (1-EGFR, 2-ERBB2, 1-ROS1, 1-RET, 2-MET, 2-KRAS and 1-MAP2K1). Primary NGS was used mainly in squamous cell cancers (SCCAs) (6/7 or 85.7%). In 7 SCCAs, 1 sample had a driver aberration (FGFR1); 6 had other genomic events (all with TP53 mutations). NGS was successful in 24/29 (82.7%) tumors overall. There was a trend toward increased assay failure in those samples undergoing sequential SGAs followed by NGS as compared to primary NGS alone. All patients with EGFR-mutated or ALK-rearranged tumors received approved tyrosine kinase inhibitors (TKIs) or were consented for clinical trials. Clinical decisions were impacted by NGS results in 8/17 (47.0%) ACs (trial consideration in 6, off-label TKI use in 2). Therapeutic decisions were influenced by NGS results in 0/7 SCCAs (p=0.0538 when compared to ACs). Actionable therapeutic targets were significantly more frequent in patients with a ≤15 pack-year tobacco history vs. those with >15 pack-years of tobacco use (17/27 or 62.9% vs. 3/42 or 7.1%, respectively; p<0.0001). Only 1/9 (11%) of oncologists demonstrated a detailed understanding of the genomic technologies being used. Figure 1
Conclusion:
Targeted NGS can identify a significant number of driver events in lung ACs—particularly in never/light smokers—for which targeted therapies are available or in development. However, for SCCAs, NGS results are less likely to alter standard practice, barring participation in biomarker-driven studies. Future research into the cost effectiveness and optimal use of NGS in NSCLC is warranted, as well as continued efforts to improve provider awareness and application of genomic technologies.
