Supplementary Table S1 from 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.; Shepherd, Frances A.; Imamura, Fumio; Cheng, Ying; Okamoto, Isamu; Cho, Byoung Chul; Lin, Meng-Chih; Wu, Yi-Long; Majem, Margarita; Gautschi, Oliver; Boyer, Michael; Bulusu, Krishna C.; Markovets, Aleksandra; Barrett, J. Carl; Hodge, Rachel; McKeown, Astrid; Hartmaier, Ryan J.; Chmielecki, Juliann; Papadimitrakopoulou, Vassiliki A.; Ramalingam, Suresh S.

doi:10.1158/1078-0432.23717517.v1

Supplementary Table S1 from 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

journal contribution

posted on 2023-07-20, 15:00 authored by 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

Representativeness of study participants

History

ARTICLE ABSTRACT

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