Early Clearance of Plasma Epidermal Growth Factor Receptor Mutations as a Predictor of Outcome on Osimertinib in Advanced Non-Small Cell Lung Cancer; Exploratory Analysis from AURA3 and FLAURA

Jhanelle E. Gray; Myung Ju Ahn; Geoffrey R. Oxnard; Frances A. Shepherd; Fumio Imamura; Ying Cheng; Isamu Okamoto; Byoung Chul Cho; Meng Chih Lin; Yi Long Wu; Margarita Majem; Oliver Gautschi; Michael Boyer; Krishna C. Bulusu; Aleksandra Markovets; J. Carl Barrett; Rachel Hodge; Astrid McKeown; Ryan J. Hartmaier; Juliann Chmielecki; Vassiliki A. Papadimitrakopoulou; Suresh S. Ramalingam

doi:10.1158/1078-0432.CCR-22-3146

Early Clearance of Plasma Epidermal Growth Factor Receptor Mutations as a Predictor of Outcome on Osimertinib in Advanced Non-Small Cell Lung Cancer; Exploratory Analysis from AURA3 and FLAURA

Jhanelle E. Gray
, Myung Ju Ahn
, Geoffrey R. Oxnard
, Frances A. Shepherd
, Fumio Imamura
, Ying Cheng
, Isamu Okamoto
, Byoung Chul Cho
, Meng Chih Lin
, Yi Long Wu
, Margarita Majem
, Oliver Gautschi
, Michael Boyer
, Krishna C. Bulusu
, Aleksandra Markovets
, J. Carl Barrett
, Rachel Hodge
, Astrid McKeown
, Ryan J. Hartmaier
, Juliann Chmielecki

Vassiliki A. Papadimitrakopoulou, Suresh S. Ramalingam^*

^*Corresponding author for this work

University of South Florida
Sungkyunkwan University
Dana-Farber Cancer Institute
University Health Network
Osaka International Cancer Institute
Jilin Provincial Cancer Hospital
Kyushu University
Yonsei University
Chang Gung University
Guangdong Academy of Medical Sciences
Hosp Santa Creu & Sant Pau
University of Bern
Chris O'Brien Lifehouse
AstraZeneca
University of Texas Health Science Center at Houston
Emory University

Research output: Contribution to journal › Journal Article › peer-review

57 Scopus citations

Abstract

PURPOSE: Plasma circulating tumor DNA (ctDNA) analysis is used for genotyping advanced non-small cell lung cancer (NSCLC); monitoring dynamic ctDNA changes may be used to predict outcomes.

PATIENTS AND METHODS: This was a retrospective, exploratory analysis of two phase III trials [AURA3 (NCT02151981), FLAURA (NCT02296125)]. All patients had EGFR mutation-positive (EGFRm; ex19del or L858R) advanced NSCLC; AURA3 also included T790M-positive NSCLC. Osimertinib (FLAURA, AURA3), or comparator EGFR-tyrosine kinase inhibitor (EGFR-TKI; gefitinib/erlotinib; FLAURA), or platinum-based doublet chemotherapy (AURA3) was given. Plasma EGFRm was analyzed at baseline and Weeks 3/6 by droplet digital PCR. Outcomes were assessed by detectable/non-detectable baseline plasma EGFRm and plasma EGFRm clearance (non-detection) at Weeks 3/6.

RESULTS: In AURA3 (n = 291), non-detectable versus detectable baseline plasma EGFRm had longer median progression-free survival [mPFS; HR, 0.48; 95% confidence interval (CI), 0.33-0.68; P < 0.0001]. In patients with Week 3 clearance versus non-clearance (n = 184), respectively, mPFS (months; 95% CI) was 10.9 (8.3-12.6) versus 5.7 (4.1-9.7) with osimertinib and 6.2 (4.0-9.7) versus 4.2 (4.0-5.1) with platinum-pemetrexed. In FLAURA (n = 499), mPFS was longer with non-detectable versus detectable baseline plasma EGFRm (HR, 0.54; 95% CI, 0.41-0.70; P < 0.0001). For Week 3 clearance versus non-clearance (n = 334), respectively, mPFS was 19.8 (15.1 to not calculable) versus 11.3 (9.5-16.5) with osimertinib and 10.8 (9.7-11.1) versus 7.0 (5.6-8.3) with comparator EGFR-TKI. Similar outcomes were observed by Week 6 clearance/non-clearance.

CONCLUSIONS: Plasma EGFRm analysis as early as 3 weeks on-treatment has the potential to predict outcomes in EGFRm advanced NSCLC.

Original language	English
Pages (from-to)	3340-3351
Number of pages	12
Journal	Clinical Cancer Research
Volume	29
Issue number	17
DOIs	https://doi.org/10.1158/1078-0432.CCR-22-3146
State	Published - 01 09 2023
Externally published	Yes

Bibliographical note

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1158/1078-0432.CCR-22-3146

Cite this

Gray, J. E., Ahn, M. J., Oxnard, G. R., Shepherd, F. A., Imamura, F., Cheng, Y., Okamoto, I., Cho, B. C., Lin, M. C., Wu, Y. L., Majem, M., Gautschi, O., Boyer, M., Bulusu, K. C., Markovets, A., Barrett, J. C., Hodge, R., McKeown, A., Hartmaier, R. J., ... Ramalingam, S. S. (2023). Early Clearance of Plasma Epidermal Growth Factor Receptor Mutations as a Predictor of Outcome on Osimertinib in Advanced Non-Small Cell Lung Cancer; Exploratory Analysis from AURA3 and FLAURA. Clinical Cancer Research, 29(17), 3340-3351. https://doi.org/10.1158/1078-0432.CCR-22-3146

@article{bfc4c714acb049749e4b75010439dfb4,

title = "Early Clearance of Plasma Epidermal Growth Factor Receptor Mutations as a Predictor of Outcome on Osimertinib in Advanced Non-Small Cell Lung Cancer; Exploratory Analysis from AURA3 and FLAURA",

abstract = "PURPOSE: Plasma circulating tumor DNA (ctDNA) analysis is used for genotyping advanced non-small cell lung cancer (NSCLC); monitoring dynamic ctDNA changes may be used to predict outcomes.PATIENTS AND METHODS: This was a retrospective, exploratory analysis of two phase III trials [AURA3 (NCT02151981), FLAURA (NCT02296125)]. All patients had EGFR mutation-positive (EGFRm; ex19del or L858R) advanced NSCLC; AURA3 also included T790M-positive NSCLC. Osimertinib (FLAURA, AURA3), or comparator EGFR-tyrosine kinase inhibitor (EGFR-TKI; gefitinib/erlotinib; FLAURA), or platinum-based doublet chemotherapy (AURA3) was given. Plasma EGFRm was analyzed at baseline and Weeks 3/6 by droplet digital PCR. Outcomes were assessed by detectable/non-detectable baseline plasma EGFRm and plasma EGFRm clearance (non-detection) at Weeks 3/6.RESULTS: In AURA3 (n = 291), non-detectable versus detectable baseline plasma EGFRm had longer median progression-free survival [mPFS; HR, 0.48; 95\% confidence interval (CI), 0.33-0.68; P < 0.0001]. In patients with Week 3 clearance versus non-clearance (n = 184), respectively, mPFS (months; 95\% CI) was 10.9 (8.3-12.6) versus 5.7 (4.1-9.7) with osimertinib and 6.2 (4.0-9.7) versus 4.2 (4.0-5.1) with platinum-pemetrexed. In FLAURA (n = 499), mPFS was longer with non-detectable versus detectable baseline plasma EGFRm (HR, 0.54; 95\% CI, 0.41-0.70; P < 0.0001). For Week 3 clearance versus non-clearance (n = 334), respectively, mPFS was 19.8 (15.1 to not calculable) versus 11.3 (9.5-16.5) with osimertinib and 10.8 (9.7-11.1) versus 7.0 (5.6-8.3) with comparator EGFR-TKI. Similar outcomes were observed by Week 6 clearance/non-clearance.CONCLUSIONS: Plasma EGFRm analysis as early as 3 weeks on-treatment has the potential to predict outcomes in EGFRm advanced NSCLC.",

author = "Gray, \{Jhanelle E.\} and Ahn, \{Myung Ju\} and Oxnard, \{Geoffrey R.\} and Shepherd, \{Frances A.\} and Fumio Imamura and Ying Cheng and Isamu Okamoto and Cho, \{Byoung Chul\} and Lin, \{Meng Chih\} and Wu, \{Yi Long\} and Margarita Majem and Oliver Gautschi and Michael Boyer and Bulusu, \{Krishna C.\} and Aleksandra Markovets and Barrett, \{J. Carl\} and Rachel Hodge and Astrid McKeown and Hartmaier, \{Ryan J.\} and Juliann Chmielecki and Papadimitrakopoulou, \{Vassiliki A.\} and Ramalingam, \{Suresh S.\}",

note = "{\textcopyright}2023 American Association for Cancer Research.",

year = "2023",

month = sep,

day = "1",

doi = "10.1158/1078-0432.CCR-22-3146",

language = "英语",

volume = "29",

pages = "3340--3351",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research Inc.",

number = "17",

}

Gray, JE, Ahn, MJ, Oxnard, GR, Shepherd, FA, Imamura, F, Cheng, Y, Okamoto, I, Cho, BC, Lin, MC, Wu, YL, Majem, M, Gautschi, O, Boyer, M, Bulusu, KC, Markovets, A, Barrett, JC, Hodge, R, McKeown, A, Hartmaier, RJ, Chmielecki, J, Papadimitrakopoulou, VA & Ramalingam, SS 2023, 'Early Clearance of Plasma Epidermal Growth Factor Receptor Mutations as a Predictor of Outcome on Osimertinib in Advanced Non-Small Cell Lung Cancer; Exploratory Analysis from AURA3 and FLAURA', Clinical Cancer Research, vol. 29, no. 17, pp. 3340-3351. https://doi.org/10.1158/1078-0432.CCR-22-3146

Early Clearance of Plasma Epidermal Growth Factor Receptor Mutations as a Predictor of Outcome on Osimertinib in Advanced Non-Small Cell Lung Cancer; Exploratory Analysis from AURA3 and FLAURA. / Gray, Jhanelle E.; Ahn, Myung Ju; Oxnard, Geoffrey R. et al.
In: Clinical Cancer Research, Vol. 29, No. 17, 01.09.2023, p. 3340-3351.

Research output: Contribution to journal › Journal Article › peer-review

TY - JOUR

T1 - Early Clearance of Plasma Epidermal Growth Factor Receptor Mutations as a Predictor of Outcome on Osimertinib in Advanced Non-Small Cell Lung Cancer; Exploratory Analysis from AURA3 and FLAURA

AU - Gray, Jhanelle E.

AU - Ahn, Myung Ju

AU - Oxnard, Geoffrey R.

AU - Shepherd, Frances A.

AU - Imamura, Fumio

AU - Cheng, Ying

AU - Okamoto, Isamu

AU - Cho, Byoung Chul

AU - Lin, Meng Chih

AU - Wu, Yi Long

AU - Majem, Margarita

AU - Gautschi, Oliver

AU - Boyer, Michael

AU - Bulusu, Krishna C.

AU - Markovets, Aleksandra

AU - Barrett, J. Carl

AU - Hodge, Rachel

AU - McKeown, Astrid

AU - Hartmaier, Ryan J.

AU - Chmielecki, Juliann

AU - Papadimitrakopoulou, Vassiliki A.

AU - Ramalingam, Suresh S.

PY - 2023/9/1

Y1 - 2023/9/1

N2 - PURPOSE: Plasma circulating tumor DNA (ctDNA) analysis is used for genotyping advanced non-small cell lung cancer (NSCLC); monitoring dynamic ctDNA changes may be used to predict outcomes.PATIENTS AND METHODS: This was a retrospective, exploratory analysis of two phase III trials [AURA3 (NCT02151981), FLAURA (NCT02296125)]. All patients had EGFR mutation-positive (EGFRm; ex19del or L858R) advanced NSCLC; AURA3 also included T790M-positive NSCLC. Osimertinib (FLAURA, AURA3), or comparator EGFR-tyrosine kinase inhibitor (EGFR-TKI; gefitinib/erlotinib; FLAURA), or platinum-based doublet chemotherapy (AURA3) was given. Plasma EGFRm was analyzed at baseline and Weeks 3/6 by droplet digital PCR. Outcomes were assessed by detectable/non-detectable baseline plasma EGFRm and plasma EGFRm clearance (non-detection) at Weeks 3/6.RESULTS: In AURA3 (n = 291), non-detectable versus detectable baseline plasma EGFRm had longer median progression-free survival [mPFS; HR, 0.48; 95% confidence interval (CI), 0.33-0.68; P < 0.0001]. In patients with Week 3 clearance versus non-clearance (n = 184), respectively, mPFS (months; 95% CI) was 10.9 (8.3-12.6) versus 5.7 (4.1-9.7) with osimertinib and 6.2 (4.0-9.7) versus 4.2 (4.0-5.1) with platinum-pemetrexed. In FLAURA (n = 499), mPFS was longer with non-detectable versus detectable baseline plasma EGFRm (HR, 0.54; 95% CI, 0.41-0.70; P < 0.0001). For Week 3 clearance versus non-clearance (n = 334), respectively, mPFS was 19.8 (15.1 to not calculable) versus 11.3 (9.5-16.5) with osimertinib and 10.8 (9.7-11.1) versus 7.0 (5.6-8.3) with comparator EGFR-TKI. Similar outcomes were observed by Week 6 clearance/non-clearance.CONCLUSIONS: Plasma EGFRm analysis as early as 3 weeks on-treatment has the potential to predict outcomes in EGFRm advanced NSCLC.

AB - PURPOSE: Plasma circulating tumor DNA (ctDNA) analysis is used for genotyping advanced non-small cell lung cancer (NSCLC); monitoring dynamic ctDNA changes may be used to predict outcomes.PATIENTS AND METHODS: This was a retrospective, exploratory analysis of two phase III trials [AURA3 (NCT02151981), FLAURA (NCT02296125)]. All patients had EGFR mutation-positive (EGFRm; ex19del or L858R) advanced NSCLC; AURA3 also included T790M-positive NSCLC. Osimertinib (FLAURA, AURA3), or comparator EGFR-tyrosine kinase inhibitor (EGFR-TKI; gefitinib/erlotinib; FLAURA), or platinum-based doublet chemotherapy (AURA3) was given. Plasma EGFRm was analyzed at baseline and Weeks 3/6 by droplet digital PCR. Outcomes were assessed by detectable/non-detectable baseline plasma EGFRm and plasma EGFRm clearance (non-detection) at Weeks 3/6.RESULTS: In AURA3 (n = 291), non-detectable versus detectable baseline plasma EGFRm had longer median progression-free survival [mPFS; HR, 0.48; 95% confidence interval (CI), 0.33-0.68; P < 0.0001]. In patients with Week 3 clearance versus non-clearance (n = 184), respectively, mPFS (months; 95% CI) was 10.9 (8.3-12.6) versus 5.7 (4.1-9.7) with osimertinib and 6.2 (4.0-9.7) versus 4.2 (4.0-5.1) with platinum-pemetrexed. In FLAURA (n = 499), mPFS was longer with non-detectable versus detectable baseline plasma EGFRm (HR, 0.54; 95% CI, 0.41-0.70; P < 0.0001). For Week 3 clearance versus non-clearance (n = 334), respectively, mPFS was 19.8 (15.1 to not calculable) versus 11.3 (9.5-16.5) with osimertinib and 10.8 (9.7-11.1) versus 7.0 (5.6-8.3) with comparator EGFR-TKI. Similar outcomes were observed by Week 6 clearance/non-clearance.CONCLUSIONS: Plasma EGFRm analysis as early as 3 weeks on-treatment has the potential to predict outcomes in EGFRm advanced NSCLC.

UR - https://www.scopus.com/pages/publications/85171599405

U2 - 10.1158/1078-0432.CCR-22-3146

DO - 10.1158/1078-0432.CCR-22-3146

M3 - 文章

C2 - 37379430

AN - SCOPUS:85171599405

SN - 1078-0432

VL - 29

SP - 3340

EP - 3351

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 17

ER -

Early Clearance of Plasma Epidermal Growth Factor Receptor Mutations as a Predictor of Outcome on Osimertinib in Advanced Non-Small Cell Lung Cancer; Exploratory Analysis from AURA3 and FLAURA

Abstract

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