Postprogression outcomes for osimertinib versu standard-of-care EGFR-TKI in patients with previously untreated EGFR-mutated advanced non–small cell lung cancer

David Planchard, Michael J. Boyer, Jong Seok Lee, Arunee Dechaphunkul, Parneet K. Cheema, Toshiaki Takahashi, Jhanelle E. Gray, Marcello Tiseo, Suresh S. Ramalingam, Alexander Todd, Astrid McKeown, Yuri Rukazenkov, Yuichiro Ohe

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Abstract

Purpose: In the phase III FLAURA study, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib significantly improved progression-free survival (PFS) versus standard-of-care (SoC) EGFR-TKI (gefitinib or erlotinib) in patients with previously untreated EGFR (exon 19 deletion or L858R) mutation-positive advanced non–small cell lung cancer (NSCLC). Interim overall survival (OS) data were encouraging, but not formally statistically significant at current maturity (25%). Here we report exploratory postprogression outcomes. Patients and Methods: Patients were randomized 1:1 to receive osimertinib (80 mg orally, once daily) or SoC EGFR-TKI (gefitinib 250 mg or erlotinib 150 mg, orally, once daily). Treatment beyond disease progression was allowed if the investigator judged ongoing clinical benefit. Patients receiving SoC EGFR-TKI could cross over to receive osimertinib after independently confirmed objective disease progression with documented postprogression T790M-positive mutation status. Results: At data cutoff (June 12, 2017), 138 of 279 (49%) and 213 of 277 (77%) patients discontinued osimertinib and SoC EGFR-TKI, respectively, of whom 82 (59%) and 129 (61%), respectively, started a subsequent treatment. Median time to discontinuation of any EGFR-TKI or death was 23.0 months [95% confidence interval (CI), 19.5–not calculable (NC)] in the osimertinib arm and 16.0 months (95% CI, 14.8–18.6) in the SoC EGFR-TKI arm. Median second PFS was not reached (95% CI, 23.7–NC) in the osimertinib arm and 20.0 months (95% CI, 18.2–NC) in the SoC EGFR-TKI arm [hazard ratio (HR), 0.58; 95% CI, 0.44–0.78; P ¼ 0.0004]. Conclusions: All postprogression endpoints showed consistent improvement with osimertinib versus SoC EGFR-TKI, providing further confidence in the interim OS data.

Original languageEnglish
Pages (from-to)2058-2063
Number of pages6
JournalClinical Cancer Research
Volume25
Issue number7
DOIs
StatePublished - 1 Apr 2019

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Standard of Care
Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Protein-Tyrosine Kinases
Confidence Intervals
Disease-Free Survival
Disease Progression
osimertinib
Mutation
Survival
Exons
Research Personnel
Therapeutics

Cite this

Planchard, David ; Boyer, Michael J. ; Lee, Jong Seok ; Dechaphunkul, Arunee ; Cheema, Parneet K. ; Takahashi, Toshiaki ; Gray, Jhanelle E. ; Tiseo, Marcello ; Ramalingam, Suresh S. ; Todd, Alexander ; McKeown, Astrid ; Rukazenkov, Yuri ; Ohe, Yuichiro. / Postprogression outcomes for osimertinib versu standard-of-care EGFR-TKI in patients with previously untreated EGFR-mutated advanced non–small cell lung cancer. In: Clinical Cancer Research. 2019 ; Vol. 25, No. 7. pp. 2058-2063.
@article{a4167d0b0ad74c8785350f107ef037c5,
title = "Postprogression outcomes for osimertinib versu standard-of-care EGFR-TKI in patients with previously untreated EGFR-mutated advanced non–small cell lung cancer",
abstract = "Purpose: In the phase III FLAURA study, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib significantly improved progression-free survival (PFS) versus standard-of-care (SoC) EGFR-TKI (gefitinib or erlotinib) in patients with previously untreated EGFR (exon 19 deletion or L858R) mutation-positive advanced non–small cell lung cancer (NSCLC). Interim overall survival (OS) data were encouraging, but not formally statistically significant at current maturity (25{\%}). Here we report exploratory postprogression outcomes. Patients and Methods: Patients were randomized 1:1 to receive osimertinib (80 mg orally, once daily) or SoC EGFR-TKI (gefitinib 250 mg or erlotinib 150 mg, orally, once daily). Treatment beyond disease progression was allowed if the investigator judged ongoing clinical benefit. Patients receiving SoC EGFR-TKI could cross over to receive osimertinib after independently confirmed objective disease progression with documented postprogression T790M-positive mutation status. Results: At data cutoff (June 12, 2017), 138 of 279 (49{\%}) and 213 of 277 (77{\%}) patients discontinued osimertinib and SoC EGFR-TKI, respectively, of whom 82 (59{\%}) and 129 (61{\%}), respectively, started a subsequent treatment. Median time to discontinuation of any EGFR-TKI or death was 23.0 months [95{\%} confidence interval (CI), 19.5–not calculable (NC)] in the osimertinib arm and 16.0 months (95{\%} CI, 14.8–18.6) in the SoC EGFR-TKI arm. Median second PFS was not reached (95{\%} CI, 23.7–NC) in the osimertinib arm and 20.0 months (95{\%} CI, 18.2–NC) in the SoC EGFR-TKI arm [hazard ratio (HR), 0.58; 95{\%} CI, 0.44–0.78; P ¼ 0.0004]. Conclusions: All postprogression endpoints showed consistent improvement with osimertinib versus SoC EGFR-TKI, providing further confidence in the interim OS data.",
author = "David Planchard and Boyer, {Michael J.} and Lee, {Jong Seok} and Arunee Dechaphunkul and Cheema, {Parneet K.} and Toshiaki Takahashi and Gray, {Jhanelle E.} and Marcello Tiseo and Ramalingam, {Suresh S.} and Alexander Todd and Astrid McKeown and Yuri Rukazenkov and Yuichiro Ohe",
year = "2019",
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doi = "10.1158/1078-0432.CCR-18-3325",
language = "English",
volume = "25",
pages = "2058--2063",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "7",

}

Planchard, D, Boyer, MJ, Lee, JS, Dechaphunkul, A, Cheema, PK, Takahashi, T, Gray, JE, Tiseo, M, Ramalingam, SS, Todd, A, McKeown, A, Rukazenkov, Y & Ohe, Y 2019, 'Postprogression outcomes for osimertinib versu standard-of-care EGFR-TKI in patients with previously untreated EGFR-mutated advanced non–small cell lung cancer', Clinical Cancer Research, vol. 25, no. 7, pp. 2058-2063. https://doi.org/10.1158/1078-0432.CCR-18-3325

Postprogression outcomes for osimertinib versu standard-of-care EGFR-TKI in patients with previously untreated EGFR-mutated advanced non–small cell lung cancer. / Planchard, David; Boyer, Michael J.; Lee, Jong Seok; Dechaphunkul, Arunee; Cheema, Parneet K.; Takahashi, Toshiaki; Gray, Jhanelle E.; Tiseo, Marcello; Ramalingam, Suresh S.; Todd, Alexander; McKeown, Astrid; Rukazenkov, Yuri; Ohe, Yuichiro.

In: Clinical Cancer Research, Vol. 25, No. 7, 01.04.2019, p. 2058-2063.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Postprogression outcomes for osimertinib versu standard-of-care EGFR-TKI in patients with previously untreated EGFR-mutated advanced non–small cell lung cancer

AU - Planchard, David

AU - Boyer, Michael J.

AU - Lee, Jong Seok

AU - Dechaphunkul, Arunee

AU - Cheema, Parneet K.

AU - Takahashi, Toshiaki

AU - Gray, Jhanelle E.

AU - Tiseo, Marcello

AU - Ramalingam, Suresh S.

AU - Todd, Alexander

AU - McKeown, Astrid

AU - Rukazenkov, Yuri

AU - Ohe, Yuichiro

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Purpose: In the phase III FLAURA study, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib significantly improved progression-free survival (PFS) versus standard-of-care (SoC) EGFR-TKI (gefitinib or erlotinib) in patients with previously untreated EGFR (exon 19 deletion or L858R) mutation-positive advanced non–small cell lung cancer (NSCLC). Interim overall survival (OS) data were encouraging, but not formally statistically significant at current maturity (25%). Here we report exploratory postprogression outcomes. Patients and Methods: Patients were randomized 1:1 to receive osimertinib (80 mg orally, once daily) or SoC EGFR-TKI (gefitinib 250 mg or erlotinib 150 mg, orally, once daily). Treatment beyond disease progression was allowed if the investigator judged ongoing clinical benefit. Patients receiving SoC EGFR-TKI could cross over to receive osimertinib after independently confirmed objective disease progression with documented postprogression T790M-positive mutation status. Results: At data cutoff (June 12, 2017), 138 of 279 (49%) and 213 of 277 (77%) patients discontinued osimertinib and SoC EGFR-TKI, respectively, of whom 82 (59%) and 129 (61%), respectively, started a subsequent treatment. Median time to discontinuation of any EGFR-TKI or death was 23.0 months [95% confidence interval (CI), 19.5–not calculable (NC)] in the osimertinib arm and 16.0 months (95% CI, 14.8–18.6) in the SoC EGFR-TKI arm. Median second PFS was not reached (95% CI, 23.7–NC) in the osimertinib arm and 20.0 months (95% CI, 18.2–NC) in the SoC EGFR-TKI arm [hazard ratio (HR), 0.58; 95% CI, 0.44–0.78; P ¼ 0.0004]. Conclusions: All postprogression endpoints showed consistent improvement with osimertinib versus SoC EGFR-TKI, providing further confidence in the interim OS data.

AB - Purpose: In the phase III FLAURA study, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib significantly improved progression-free survival (PFS) versus standard-of-care (SoC) EGFR-TKI (gefitinib or erlotinib) in patients with previously untreated EGFR (exon 19 deletion or L858R) mutation-positive advanced non–small cell lung cancer (NSCLC). Interim overall survival (OS) data were encouraging, but not formally statistically significant at current maturity (25%). Here we report exploratory postprogression outcomes. Patients and Methods: Patients were randomized 1:1 to receive osimertinib (80 mg orally, once daily) or SoC EGFR-TKI (gefitinib 250 mg or erlotinib 150 mg, orally, once daily). Treatment beyond disease progression was allowed if the investigator judged ongoing clinical benefit. Patients receiving SoC EGFR-TKI could cross over to receive osimertinib after independently confirmed objective disease progression with documented postprogression T790M-positive mutation status. Results: At data cutoff (June 12, 2017), 138 of 279 (49%) and 213 of 277 (77%) patients discontinued osimertinib and SoC EGFR-TKI, respectively, of whom 82 (59%) and 129 (61%), respectively, started a subsequent treatment. Median time to discontinuation of any EGFR-TKI or death was 23.0 months [95% confidence interval (CI), 19.5–not calculable (NC)] in the osimertinib arm and 16.0 months (95% CI, 14.8–18.6) in the SoC EGFR-TKI arm. Median second PFS was not reached (95% CI, 23.7–NC) in the osimertinib arm and 20.0 months (95% CI, 18.2–NC) in the SoC EGFR-TKI arm [hazard ratio (HR), 0.58; 95% CI, 0.44–0.78; P ¼ 0.0004]. Conclusions: All postprogression endpoints showed consistent improvement with osimertinib versus SoC EGFR-TKI, providing further confidence in the interim OS data.

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U2 - 10.1158/1078-0432.CCR-18-3325

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VL - 25

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