Tissue and plasma EGFR mutation analysis in the FLAURA trial: Osimertinib versus Comparator EGFR tyrosine kinase inhibitor as first-line treatment in patients with EGFR-mutated advanced non–small cell lung cancer

Jhanelle E. Gray, Isamu Okamoto, Virote Sriuranpong, Johan Vansteenkiste, Fumio Imamura, Jong Seok Lee, Yong Kek Pang, Manuel Cobo, Kazuo Kasahara, Ying Cheng, Naoyuki Nogami, Eun Kyung Cho, Wu Chou Su, Guili Zhang, Xiangning Huang, Xiaocheng Li-Sucholeiki, Brian Lentrichia, Simon Dearden, Suzanne Jenkins, Matilde SaggeseYuri Rukazenkov, Suresh S. Ramalingam

Research output: Contribution to journalArticle

Abstract

Purpose: To assess the utility of the cobas EGFR Mutation Test, with tissue and plasma, for first-line osimertinib therapy for patients with EGFR-mutated (EGFRm; Ex19del and/or L858R) advanced or metastatic non–small cell lung cancer (NSCLC) from the FLAURA study (NCT02296125). Experimental Design: Tumor tissue EGFRm status was determined at screening using the central cobas tissue test or a local tissue test. Baseline circulating tumor (ct)DNA EGFRm status was retrospectively determined with the central cobas plasma test. Results: Of 994 patients screened, 556 were randomized (289 and 267 with central and local EGFR test results, respectively) and 438 failed screening. Of those randomized from local EGFR test results, 217 patients had available central test results; 211/217 (97%) were retrospectively confirmed EGFRm positive by central cobas tissue test. Using reference central cobas tissue test results, positive percent agreements with cobas plasma test results for Ex19del and L858R detection were 79% [95% confidence interval (CI), 74–84] and 68% (95% CI, 61–75), respectively. Progression-free survival (PFS) superiority with osimertinib over comparator EGFR-TKI remained consistent irrespective of randomization route (central/local EGFRm-positive tissue test). In both treatment arms, PFS was prolonged in plasma ctDNA EGFRm-negative (23.5 and 15.0 months) versus -positive patients (15.2 and 9.7 months). Conclusions: Our results support utility of cobas tissue and plasma testing to aid selection of patients with EGFRm advanced NSCLC for first-line osimertinib treatment. Lack of EGFRm detection in plasma was associated with prolonged PFS versus patients plasma EGFRm positive, potentially due to patients having lower tumor burden.

Original languageEnglish
Pages (from-to)6644-6652
Number of pages9
JournalClinical Cancer Research
Volume25
Issue number22
DOIs
Publication statusPublished - Nov 15 2019

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Non-Small Cell Lung Carcinoma
Protein-Tyrosine Kinases
Mutation
Disease-Free Survival
Therapeutics
Confidence Intervals
osimertinib
Random Allocation
Tumor Burden
Patient Selection
Neoplasms
Research Design
DNA

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Tissue and plasma EGFR mutation analysis in the FLAURA trial : Osimertinib versus Comparator EGFR tyrosine kinase inhibitor as first-line treatment in patients with EGFR-mutated advanced non–small cell lung cancer. / Gray, Jhanelle E.; Okamoto, Isamu; Sriuranpong, Virote; Vansteenkiste, Johan; Imamura, Fumio; Lee, Jong Seok; Pang, Yong Kek; Cobo, Manuel; Kasahara, Kazuo; Cheng, Ying; Nogami, Naoyuki; Cho, Eun Kyung; Su, Wu Chou; Zhang, Guili; Huang, Xiangning; Li-Sucholeiki, Xiaocheng; Lentrichia, Brian; Dearden, Simon; Jenkins, Suzanne; Saggese, Matilde; Rukazenkov, Yuri; Ramalingam, Suresh S.

In: Clinical Cancer Research, Vol. 25, No. 22, 15.11.2019, p. 6644-6652.

Research output: Contribution to journalArticle

Gray, JE, Okamoto, I, Sriuranpong, V, Vansteenkiste, J, Imamura, F, Lee, JS, Pang, YK, Cobo, M, Kasahara, K, Cheng, Y, Nogami, N, Cho, EK, Su, WC, Zhang, G, Huang, X, Li-Sucholeiki, X, Lentrichia, B, Dearden, S, Jenkins, S, Saggese, M, Rukazenkov, Y & Ramalingam, SS 2019, 'Tissue and plasma EGFR mutation analysis in the FLAURA trial: Osimertinib versus Comparator EGFR tyrosine kinase inhibitor as first-line treatment in patients with EGFR-mutated advanced non–small cell lung cancer', Clinical Cancer Research, vol. 25, no. 22, pp. 6644-6652. https://doi.org/10.1158/1078-0432.CCR-19-1126
Gray, Jhanelle E. ; Okamoto, Isamu ; Sriuranpong, Virote ; Vansteenkiste, Johan ; Imamura, Fumio ; Lee, Jong Seok ; Pang, Yong Kek ; Cobo, Manuel ; Kasahara, Kazuo ; Cheng, Ying ; Nogami, Naoyuki ; Cho, Eun Kyung ; Su, Wu Chou ; Zhang, Guili ; Huang, Xiangning ; Li-Sucholeiki, Xiaocheng ; Lentrichia, Brian ; Dearden, Simon ; Jenkins, Suzanne ; Saggese, Matilde ; Rukazenkov, Yuri ; Ramalingam, Suresh S. / Tissue and plasma EGFR mutation analysis in the FLAURA trial : Osimertinib versus Comparator EGFR tyrosine kinase inhibitor as first-line treatment in patients with EGFR-mutated advanced non–small cell lung cancer. In: Clinical Cancer Research. 2019 ; Vol. 25, No. 22. pp. 6644-6652.
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abstract = "Purpose: To assess the utility of the cobas EGFR Mutation Test, with tissue and plasma, for first-line osimertinib therapy for patients with EGFR-mutated (EGFRm; Ex19del and/or L858R) advanced or metastatic non–small cell lung cancer (NSCLC) from the FLAURA study (NCT02296125). Experimental Design: Tumor tissue EGFRm status was determined at screening using the central cobas tissue test or a local tissue test. Baseline circulating tumor (ct)DNA EGFRm status was retrospectively determined with the central cobas plasma test. Results: Of 994 patients screened, 556 were randomized (289 and 267 with central and local EGFR test results, respectively) and 438 failed screening. Of those randomized from local EGFR test results, 217 patients had available central test results; 211/217 (97{\%}) were retrospectively confirmed EGFRm positive by central cobas tissue test. Using reference central cobas tissue test results, positive percent agreements with cobas plasma test results for Ex19del and L858R detection were 79{\%} [95{\%} confidence interval (CI), 74–84] and 68{\%} (95{\%} CI, 61–75), respectively. Progression-free survival (PFS) superiority with osimertinib over comparator EGFR-TKI remained consistent irrespective of randomization route (central/local EGFRm-positive tissue test). In both treatment arms, PFS was prolonged in plasma ctDNA EGFRm-negative (23.5 and 15.0 months) versus -positive patients (15.2 and 9.7 months). Conclusions: Our results support utility of cobas tissue and plasma testing to aid selection of patients with EGFRm advanced NSCLC for first-line osimertinib treatment. Lack of EGFRm detection in plasma was associated with prolonged PFS versus patients plasma EGFRm positive, potentially due to patients having lower tumor burden.",
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T1 - Tissue and plasma EGFR mutation analysis in the FLAURA trial

T2 - Osimertinib versus Comparator EGFR tyrosine kinase inhibitor as first-line treatment in patients with EGFR-mutated advanced non–small cell lung cancer

AU - Gray, Jhanelle E.

AU - Okamoto, Isamu

AU - Sriuranpong, Virote

AU - Vansteenkiste, Johan

AU - Imamura, Fumio

AU - Lee, Jong Seok

AU - Pang, Yong Kek

AU - Cobo, Manuel

AU - Kasahara, Kazuo

AU - Cheng, Ying

AU - Nogami, Naoyuki

AU - Cho, Eun Kyung

AU - Su, Wu Chou

AU - Zhang, Guili

AU - Huang, Xiangning

AU - Li-Sucholeiki, Xiaocheng

AU - Lentrichia, Brian

AU - Dearden, Simon

AU - Jenkins, Suzanne

AU - Saggese, Matilde

AU - Rukazenkov, Yuri

AU - Ramalingam, Suresh S.

PY - 2019/11/15

Y1 - 2019/11/15

N2 - Purpose: To assess the utility of the cobas EGFR Mutation Test, with tissue and plasma, for first-line osimertinib therapy for patients with EGFR-mutated (EGFRm; Ex19del and/or L858R) advanced or metastatic non–small cell lung cancer (NSCLC) from the FLAURA study (NCT02296125). Experimental Design: Tumor tissue EGFRm status was determined at screening using the central cobas tissue test or a local tissue test. Baseline circulating tumor (ct)DNA EGFRm status was retrospectively determined with the central cobas plasma test. Results: Of 994 patients screened, 556 were randomized (289 and 267 with central and local EGFR test results, respectively) and 438 failed screening. Of those randomized from local EGFR test results, 217 patients had available central test results; 211/217 (97%) were retrospectively confirmed EGFRm positive by central cobas tissue test. Using reference central cobas tissue test results, positive percent agreements with cobas plasma test results for Ex19del and L858R detection were 79% [95% confidence interval (CI), 74–84] and 68% (95% CI, 61–75), respectively. Progression-free survival (PFS) superiority with osimertinib over comparator EGFR-TKI remained consistent irrespective of randomization route (central/local EGFRm-positive tissue test). In both treatment arms, PFS was prolonged in plasma ctDNA EGFRm-negative (23.5 and 15.0 months) versus -positive patients (15.2 and 9.7 months). Conclusions: Our results support utility of cobas tissue and plasma testing to aid selection of patients with EGFRm advanced NSCLC for first-line osimertinib treatment. Lack of EGFRm detection in plasma was associated with prolonged PFS versus patients plasma EGFRm positive, potentially due to patients having lower tumor burden.

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