Oncology and Therapy (Mar 2024)

The Impact of Prior Single-Gene Testing on Comprehensive Genomic Profiling Results for Patients with Non-Small Cell Lung Cancer

  • Mary K. Nesline,
  • Vivek Subbiah,
  • Rebecca A. Previs,
  • Kyle C. Strickland,
  • Heidi Ko,
  • Paul DePietro,
  • Michael D. Biorn,
  • Maureen Cooper,
  • Nini Wu,
  • Jeffrey Conroy,
  • Sarabjot Pabla,
  • Shengle Zhang,
  • Zachary D. Wallen,
  • Pratheesh Sathyan,
  • Kamal Saini,
  • Marcia Eisenberg,
  • Brian Caveney,
  • Eric A. Severson,
  • Shakti Ramkissoon

DOI
https://doi.org/10.1007/s40487-024-00270-x
Journal volume & issue
Vol. 12, no. 2
pp. 329 – 343

Abstract

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Abstract Introduction Tissue-based broad molecular profiling of guideline-recommended biomarkers is advised for the therapeutic management of patients with non-small cell lung cancer (NSCLC). However, practice variation can affect whether all indicated biomarkers are tested. We aimed to evaluate the impact of common single-gene testing (SGT) on subsequent comprehensive genomic profiling (CGP) test outcomes and results in NSCLC. Methods Oncologists who ordered SGT for guideline-recommended biomarkers in NSCLC patients were prospectively contacted (May–December 2022) and offered CGP (DNA and RNA sequencing), either following receipt of negative SGT findings, or instead of SGT for each patient. We describe SGT patterns and compare CGP completion rates, turnaround time, and recommended biomarker detection for NSCLC patients with and without prior negative SGT results. Results Oncologists in > 80 community practices ordered CGP for 561 NSCLC patients; 135 patients (27%) first had negative results from 30 different SGT combinations; 84% included ALK, EGFR and PD-L1, while only 3% of orders included all available SGTs for guideline-recommended genes. Among patients with negative SGT results, CGP was attempted using the same tissue specimen 90% of the time. There were also significantly more CGP order cancellations due to tissue insufficiency (17% vs. 7%), DNA sequencing failures (13% vs. 8%), and turnaround time > 14 days (62% vs. 29%) than among patients who only had CGP. Forty-six percent of patients with negative prior SGT had positive CGP results for recommended biomarkers, including targetable genomic variants in genes beyond ALK and EGFR, such as ERBB2, KRAS (non-G12C), MET (exon 14 skipping), NTRK2/3, and RET . Conclusion For patients with NSCLC, initial use of SGT increases subsequent CGP test cancellations, turnaround time, and the likelihood of incomplete molecular profiling for guideline-recommended biomarkers due to tissue insufficiency.

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