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Updated: Mar 1, 2026
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer
Glen J Weiss1,2, Sara A Byron2, Jessica Aldrich2
1Western Regional Medical Center, Cancer Treatment Centers of America, Goodyear, Arizona, United States of America.
Background:
Small cell lung cancer (SCLC) that has progressed after first-line therapy is an aggressive disease with few effective therapeutic strategies. In this prospective study, we employed next-generation sequencing (NGS) to identify therapeutically actionable alterations to guide treatment for advanced SCLC patients.
Methods:
Twelve patients with SCLC were enrolled after failing platinum-based chemotherapy. Following informed consent, genome-wide exome and RNA-sequencing was performed in a CLIA-certified, CAP-accredited environment. Actionable targets were identified and therapeutic recommendations made from a pharmacopeia of FDA-approved drugs. Clinical response to genomically-guided treatment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Results:
The study completed its accrual goal of 12 evaluable patients. The minimum tumor content for successful NGS was 20%, with a median turnaround time from sample collection to genomics-based treatment recommendation of 27 days. At least two clinically actionable targets were identified in each patient, and six patients (50%) received treatment identified by NGS. Two had partial responses by RECIST 1.1 on a clinical trial involving a PD-1 inhibitor + irinotecan (indicated by MLH1 alteration). The remaining patients had clinical deterioration before NGS recommended therapy could be initiated.
Conclusions:
Comprehensive genomic profiling using NGS identified clinically-actionable alterations in SCLC patients who progressed on initial therapy. Recommended PD-1 therapy generated partial responses in two patients. Earlier access to NGS guided therapy, along with improved understanding of those SCLC patients likely to respond to immune-based therapies, should help to extend survival in these cases with poor outcomes.
Insights
Next-generation sequencing (NGS) identified actionable targets in advanced small cell lung cancer (SCLC) patients. Genomically-guided therapy showed partial responses in 50% of treated patients, highlighting NGS potential for poor-prognosis SCLC.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Small cell lung cancer (SCLC) progressing after first-line therapy presents an aggressive clinical challenge with limited treatment options.
- Identifying therapeutically actionable alterations is crucial for guiding treatment in advanced SCLC.
Purpose of the Study:
- To employ next-generation sequencing (NGS) for identifying actionable genomic alterations in advanced SCLC patients.
- To guide subsequent treatment decisions based on identified targets.
Main Methods:
- Prospective study of 12 SCLC patients post-platinum-based chemotherapy.
- Genome-wide exome and RNA-sequencing performed in a CLIA-certified, CAP-accredited setting.
- Actionable targets identified to guide treatment with FDA-approved drugs; response assessed by RECIST 1.1.
Main Results:
- Accrual goal of 12 patients met; minimum 20% tumor content required for successful NGS.
- Median turnaround time from sample collection to recommendation was 27 days.
- Each patient had at least two actionable targets; 50% received NGS-guided treatment, with two partial responses (PD-1 inhibitor + irinotecan for MLH1 alteration).
Conclusions:
- Comprehensive genomic profiling via NGS successfully identified actionable alterations in advanced SCLC.
- PD-1 inhibitor therapy guided by NGS resulted in partial responses in two patients.
- Earlier access to NGS and better prediction of response to immunotherapy may improve survival in SCLC.
