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

被引：29

作者：

Gray, Jhanelle E. ^{[1
]}

Ahn, Myung-Ju ^{[2
]}

Oxnard, Geoffrey R. ^{[3
]}

Shepherd, Frances A. ^{[4
]}

Imamura, Fumio ^{[5
]}

Cheng, Ying ^{[6
]}

Okamoto, Isamu ^{[7
]}

Cho, Byoung Chul ^{[8
]}

Lin, Meng-Chih ^{[9
]}

Wu, Yi-Long ^{[10
]}

Majem, Margarita ^{[11
]}

Gautschi, Oliver ^{[12
,13
]}

Boyer, Michael ^{[14
]}

Bulusu, Krishna C. ^{[15
]}

Markovets, Aleksandra ^{[16
]}

Barrett, J. Carl ^{[16
]}

Hodge, Rachel ^{[17
]}

Mckeown, Astrid ^{[18
]}

Hartmaier, Ryan J. ^{[16
]}

Chmielecki, Juliann ^{[16
]}

Papadimitrakopoulou, Vassiliki A. ^{[19
]}

Ramalingam, Suresh S. ^{[20
,21
]}

机构：

[1] H Lee Moffitt Canc Ctr & Res Inst, Dept Thorac Oncol, Tampa, FL USA

[2] Sungkyunkwan Univ, Sect Hematol Oncol, Samsung Med Ctr, Sch Med, Seoul, South Korea

[3] Dana Farber Canc Inst, Boston, MA USA

[4] Princess Margaret Canc Ctr, Toronto, ON, Canada

[5] Osaka Int Canc Inst, Dept Thorac Oncol, Osaka, Japan

[6] Canc Hosp Jilin Prov, Dept Oncol, Changchun, Peoples R China

[7] Kyushu Univ, Grad Sch Med Sci, Dept Resp Med, Fukuoka, Japan

[8] Yonsei Univ, Yonsei Canc Ctr, Div Med Oncol, Coll Med, Seoul, South Korea

[9] Chang Gung Univ, Kaohsiung Chang Gung Mem Hosp, Div Pulm & Crit Care Med, Kaohsiung, Taiwan

[10] Guangdong Prov Peoples Hosp & Guangdong Acad Med S, Guangdong Lung Canc Inst, Guangzhou, Peoples R China

[11] Hosp Santa Creu & Sant Pau, Dept Resp Med, Barcelona, Spain

[12] Univ Bern, Luzern, Switzerland

[13] Cantonal Hosp Lucerne, Luzern, Switzerland

[14] Chris OBrien Lifehouse, Dept Med Oncol, Camperdown, NSW, Australia

[15] AstraZeneca, R&D Oncol, Translat Med, Cambridge, England

[16] AstraZeneca, Oncol R&D, Translat Med, Boston, MA USA

[17] AstraZeneca, Late Oncol Stat, Oncol R&D, Cambridge, England

[18] AstraZeneca, Clin Dev, Oncol R&D, Cambridge, England

[19] Univ Texas MD Anderson Canc Ctr, Houston, TX USA

[20] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA

[21] Emory Univ, Winship Canc Inst, 1365 Clifton Rd NE, Atlanta, GA 30322 USA

来源：

CLINICAL CANCER RESEARCH | 2023年 / 29卷 / 17期

关键词：

CIRCULATING TUMOR DNA; EGFR TKI; SURVIVAL; INHIBITORS; EFFICACY;

D O I：

10.1158/1078-0432.CCR-22-3146

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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/erloti nib; 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.

引用

页码：3340 / 3351

页数：12

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