Clinical Outcomes in Non-Small-Cell Lung Cancer Patients Treated With EGFR-Tyrosine Kinase Inhibitors and Other Targeted Therapies Based on Tumor Versus Plasma Genomic Profiling.

Abstract

PURPOSE:

To compare clinical outcomes in a cohort of patients with advanced non-small-cell lung cancer (NSCLC) with targetable genomic alterations detected using plasma-based circulating tumor DNA (ctDNA) or tumor-based next-generation sequencing (NGS) assays treated with US Food and Drug Administration-approved therapies at a large academic research cancer center.

METHODS:

A retrospective review from our MD Anderson GEMINI database identified 2,224 blood samples sent for ctDNA NGS testing from 1971 consecutive patients with a diagnosis of advanced NSCLC. Clinical, treatment, and outcome information were collected, reviewed, and analyzed.

RESULTS:

Overall, 27% of the ctDNA tests identified at least one targetable mutation and 73% of targetable mutations were EGFR-sensitizing mutations. Among patients treated with first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapies, there were no significant differences in progression-free survival of 379 days and 352 days (P value = .41) with treatment based on tissue (n = 40) or ctDNA (n = 40), respectively. Additionally, there were no differences in progression-free survival or objective response rate among those with low (n = 8, 0.01%-0.99%) versus high (n = 16, ≥ 1%) levels of ctDNA of the targetable mutation as measured by variant allele frequency (VAF). Overall, there was excellent testing concordance (n = 217 tests) of > 97%, sensitivity of 91.7%, and specificity of 99.7% between blood-based ctDNA NGS and tissue-based NGS assays.

CONCLUSION:

There were no significant differences in clinical outcomes among patients treated with approved EGFR-TKIs whose mutations were identified using either tumor- or plasma-based comprehensive profiling and those with very low VAF as compared with high VAF, supporting the use of plasma-based profiling to guide initial TKI use in patients with metastatic EGFR-mutant NSCLC.

• Authors: Hai T Tran, Vincent K Lam, Yasir Y Elamin, Lingzhi Hong, Rivka Colen, Nabil A Elshafeey, Islam S A Hassan, Mehmet Altan, George R Blumenschein, Waree Rinsurongkawong, Melvin J Rivera, Mayra E Vasquez, Brett W Carter, Lauren E Byers, Anne S Tsao, Don L Gibbons, Frank Fossella, Bonnie S Glisson, Jianjun Zhang, John V Heymach
• Journal: JCO precision oncology (JCO Precis Oncol) Vol. 5 (08 2021) ISSN: 2473-4284 [Electronic] United States
• PMID: 34377884 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 by American Society of Clinical Oncology.

Chemical References

• Circulating Tumor DNA
• Protein Kinase Inhibitors
• EGFR protein, human
• ErbB Receptors

Topics

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Non-Small-Cell Lung (blood, drug therapy, genetics)
• Circulating Tumor DNA (blood)
• Drug Resistance, Neoplasm (genetics)
• ErbB Receptors (genetics)
• Female
• Gene Frequency
• Genes, erbB (genetics)
• Genomics
• High-Throughput Nucleotide Sequencing
• Humans
• Lung Neoplasms (blood, drug therapy, genetics)
• Male
• Middle Aged
• Mutation
• Progression-Free Survival
• Protein Kinase Inhibitors (therapeutic use)
• Retrospective Studies