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

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, 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

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.

Conflict of interest statement

Hai T. Tran Research Funding: Bayer, Guardant Health, ZIOPHARM Oncology, Bristol Myers Squibb Vincent K. Lam Consulting or Advisory Role: Takeda, Seattle Genetics, Bristol Myers Squibb Research Funding: Guardant Health, Takeda, GlaxoSmithKline, Bristol Myers Squibb Yasir Y. Elamin Consulting or Advisory Role: Lilly, AstraZeneca, Turning Point Therapeutics Research Funding: Spectrum Pharmaceuticals, AstraZeneca, Takeda, Xcovery, Lilly, Elevation Oncology, Turning Point Therapeutics Travel, Accommodations, Expenses: Lilly Islam S. A. Hassan Employment: Agios, Servier Stock and Other Ownership Interests: Agios Mehmet Altan Consulting or Advisory Role: GlaxoSmithKline, Shattuck Labs Research Funding: Lilly, Bristol Myers Squibb, Novartis, GlaxoSmithKline, Jounce Therapeutics, Adaptimmune, Merck, Genentech, Nektar, Shattuck Labs George R. Blumenschein Employment: Janssen, Johnson & Johnson Stock and Other Ownership Interests: Virogin Biotech Consulting or Advisory Role: Bristol Myers Squibb, Bayer, Celgene, Clovis Oncology, AbbVie, ARIAD, Merck, Genentech, Novartis, Xcovery, Adicet Bio, Amgen, AstraZeneca, Roche, MedImmune, Maverick Therapeutics, Johnson & Johnson, Virogin Biotech, Gilead Sciences, Daiichi Sankyo Inc Research Funding: Merck, Celgene, Genentech, Xcovery, Novartis, Bristol Myers Squibb, GlaxoSmithKline, Adaptimmune, Macrogenics, Kite, a Gilead Company, Immatics, Torque, Incyte, MedImmune, Exelixis, Immunocore, Roche, AstraZeneca, Bayer, Tmunity Therapeutics Inc, Regeneron, BeiGene, Repertoire Immune Medicines, Daiichi Sankyo Inc Lauren E. Byers Consulting or Advisory Role: AbbVie, AstraZeneca, PharmaMar, Genmab, Bristol Myers Squibb, Sierra Oncology, Pfizer, Merck, Jazz Pharmaceuticals, Genentech, Alethia, Debiopharm Group, Tolero Pharmaceuticals Research Funding: Genmab, AstraZeneca, Sierra Oncology, Tolero Pharmaceuticals Anne S. Tsao Consulting or Advisory Role: Novartis, Boehringer Ingelheim, Genentech/Roche, Lilly, Bristol Myers Squibb, Epizyme, AstraZeneca/MedImmune, ARIAD, EMD Serono, Takeda, Heron Research Funding: Merck, Genentech/Roche, Seattle Genetics, Millennium, Bristol Myers Squibb, Boehringer Ingelheim, Polaris, EMD Serono, Seattle Genetics, Takeda Patents, Royalties, Other Intellectual Property: UptoDate Don L. Gibbons Stock and Other Ownership Interests: Exact Sciences, Nektar Consulting or Advisory Role: Sanofi, GlaxoSmithKline, Janssen Research & Development, Ribon Therapeutics, Mitobridge, Lilly, Menarini Research Funding: Janssen Research & Development, Takeda, AstraZeneca, Mitobridge, Ribon Therapeutics, Boehringer Ingelheim, Mirati Therapeutics Travel, Accommodations, Expenses: AstraZeneca/MedImmune, BerGenBio, Takeda Bonnie S. Glisson Research Funding: Pfizer, Medimmune, ISA Pharmaceuticals, CUE Biopharma Travel, Accommodations, Expenses: AbbVie/Stemcentrx, ISA Pharmaceuticals Jianjun Zhang Honoraria: Roche, Sino-USA Biomedical Platform, Geneplus, Origimed, Innovent Biologics, CancerNet, Zhejiang Cancer Hospital, Geneplus Consulting or Advisory Role: AstraZeneca, Geneplus, Capital Medical University, Johnson & Johnson/Janssen Research Funding: Merck Travel, Accommodations, Expenses: Innovent Biologics, Zhejiang Cancer Hospital John V. Heymach Stock and Other Ownership Interests: Cardinal Spine, Bio-Tree Consulting or Advisory Role: AstraZeneca, Bristol Myers Squibb, Spectrum Pharmaceuticals, Guardant Health, Hengrui Pharmaceutical, GlaxoSmithKline, EMD Serono, Lilly, Takeda, Sanofi/Aventis, Genentech/Roche, Boehringer Ingelheim, Catalyst Biotech, Foundation Medicine, Novartis, Mirati Therapeutics, BrightPath Biotheraputics, Janssen, Nexus Health Systems, Pneuma Respiratory, Kairos Ventures, Roche, Leads Biolabs Research Funding: AstraZeneca, Spectrum Pharmaceuticals, GlaxoSmithKline Patents, Royalties, Other Intellectual Property: Licensing agreement between Spectrum and MD Anderson (including myself) regarding intellectual property for treatment of EGFR and HER2 exon 20 mutations No other potential conflicts of interest were reported. Hai T. Tran Research Funding: Bayer, Guardant Health, ZIOPHARM Oncology, Bristol Myers Squibb Vincent K. Lam Consulting or Advisory Role: Takeda, Seattle Genetics, Bristol Myers Squibb Research Funding: Guardant Health, Takeda, GlaxoSmithKline, Bristol Myers Squibb Yasir Y. Elamin Consulting or Advisory Role: Lilly, AstraZeneca, Turning Point Therapeutics Research Funding: Spectrum Pharmaceuticals, AstraZeneca, Takeda, Xcovery, Lilly, Elevation Oncology, Turning Point Therapeutics Travel, Accommodations, Expenses: Lilly Islam S. A. Hassan Employment: Agios, Servier Stock and Other Ownership Interests: Agios Mehmet Altan Consulting or Advisory Role: GlaxoSmithKline, Shattuck Labs Research Funding: Lilly, Bristol Myers Squibb, Novartis, GlaxoSmithKline, Jounce Therapeutics, Adaptimmune, Merck, Genentech, Nektar, Shattuck Labs George R. Blumenschein Employment: Janssen, Johnson & Johnson Stock and Other Ownership Interests: Virogin Biotech Consulting or Advisory Role: Bristol Myers Squibb, Bayer, Celgene, Clovis Oncology, AbbVie, ARIAD, Merck, Genentech, Novartis, Xcovery, Adicet Bio, Amgen, AstraZeneca, Roche, MedImmune, Maverick Therapeutics, Johnson & Johnson, Virogin Biotech, Gilead Sciences, Daiichi Sankyo Inc Research Funding: Merck, Celgene, Genentech, Xcovery, Novartis, Bristol Myers Squibb, GlaxoSmithKline, Adaptimmune, Macrogenics, Kite, a Gilead Company, Immatics, Torque, Incyte, MedImmune, Exelixis, Immunocore, Roche, AstraZeneca, Bayer, Tmunity Therapeutics Inc, Regeneron, BeiGene, Repertoire Immune Medicines, Daiichi Sankyo Inc Lauren E. Byers Consulting or Advisory Role: AbbVie, AstraZeneca, PharmaMar, Genmab, Bristol Myers Squibb, Sierra Oncology, Pfizer, Merck, Jazz Pharmaceuticals, Genentech, Alethia, Debiopharm Group, Tolero Pharmaceuticals Research Funding: Genmab, AstraZeneca, Sierra Oncology, Tolero Pharmaceuticals Anne S. Tsao Consulting or Advisory Role: Novartis, Boehringer Ingelheim, Genentech/Roche, Lilly, Bristol Myers Squibb, Epizyme, AstraZeneca/MedImmune, ARIAD, EMD Serono, Takeda, Heron Research Funding: Merck, Genentech/Roche, Seattle Genetics, Millennium, Bristol Myers Squibb, Boehringer Ingelheim, Polaris, EMD Serono, Seattle Genetics, Takeda Patents, Royalties, Other Intellectual Property: UptoDate Don L. Gibbons Stock and Other Ownership Interests: Exact Sciences, Nektar Consulting or Advisory Role: Sanofi, GlaxoSmithKline, Janssen Research & Development, Ribon Therapeutics, Mitobridge, Lilly, Menarini Research Funding: Janssen Research & Development, Takeda, AstraZeneca, Mitobridge, Ribon Therapeutics, Boehringer Ingelheim, Mirati Therapeutics Travel, Accommodations, Expenses: AstraZeneca/MedImmune, BerGenBio, Takeda Bonnie S. Glisson Research Funding: Pfizer, Medimmune, ISA Pharmaceuticals, CUE Biopharma Travel, Accommodations, Expenses: AbbVie/Stemcentrx, ISA Pharmaceuticals Jianjun Zhang Honoraria: Roche, Sino-USA Biomedical Platform, Geneplus, Origimed, Innovent Biologics, CancerNet, Zhejiang Cancer Hospital, Geneplus Consulting or Advisory Role: AstraZeneca, Geneplus, Capital Medical University, Johnson & Johnson/Janssen Research Funding: Merck Travel, Accommodations, Expenses: Innovent Biologics, Zhejiang Cancer Hospital John V. Heymach Stock and Other Ownership Interests: Cardinal Spine, Bio-Tree Consulting or Advisory Role: AstraZeneca, Bristol Myers Squibb, Spectrum Pharmaceuticals, Guardant Health, Hengrui Pharmaceutical, GlaxoSmithKline, EMD Serono, Lilly, Takeda, Sanofi/Aventis, Genentech/Roche, Boehringer Ingelheim, Catalyst Biotech, Foundation Medicine, Novartis, Mirati Therapeutics, BrightPath Biotheraputics, Janssen, Nexus Health Systems, Pneuma Respiratory, Kairos Ventures, Roche, Leads Biolabs Research Funding: AstraZeneca, Spectrum Pharmaceuticals, GlaxoSmithKline Patents, Royalties, Other Intellectual Property: Licensing agreement between Spectrum and MD Anderson (including myself) regarding intellectual property for treatment of EGFR and HER2 exon 20 mutations No other potential conflicts of interest were reported.

© 2021 by American Society of Clinical Oncology.

Figures

FIG 1.
FIG 1.
PFS in patients with advanced non–small-cell lung cancer treated with US Food and Drug Administration–approved frontline epidermal growth factor receptor-tyrosine kinase inhibitor directed by genomic profiling from tissue-based (blue) versus ctDNA-based (red) testing, log-rank test. ctDNA, circulating tumor DNA; HR, hazard ratio; PFS, progression-free survival.
FIG 2.
FIG 2.
Comparison of clinical responses from patients with advanced NSCLC treated with FDA-approved EGFR-TKI in first line on the basis of ctDNA-identified molecular alterations. (A) Tumor responses (RECIST V1.1) on the basis of low (0.01%-0.99%, blue circle) versus high (≥ 1.00%, red box) VAF, unpaired t test. (B) PFS of low VAF (blue) and high VAF (red), log-rank test. ctDNA, circulating tumor DNA; EGFR, epidermal growth factor receptor; FDA, US Food and Drug Administration; NSCLC, non–small-cell lung cancer; PFS, progression-free survival; TKI, tyrosine kinase inhibitor; VAF, variant allele frequency.

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Source: PubMed

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