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

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.

Conflict of interest statement

Disclosure of Potential Conflicts of Interest

J.E. Gray is a consultant/advisory board member for AstraZeneca, Janssen, Genentech, Eli Lilly, Celgene, and Takeda; reports her institution receiving commercial research grants from AstraZeneca, Array, Merck, Epic Sciences, Genentech, Bristol-Myers Squibb, Boehringer Ingelheim, Trovagene, and Novartis; and reports receiving commercial research support from Genentech, AstraZeneca, Merck, Eli Lilly, and Grand Rounds. I. Okamoto reports receiving speakers bureau honoraria from AstraZeneca. J. Vansteenkiste is a consultant/advisory board member for AstraZeneca. Y.-K. Pang reports receiving speakers bureau honoraria from AstraZeneca. K. Kasahara reports receiving speakers bureau honoraria from AstraZeneca, MSD, Chugai Pharmaceuticals, and Eli Lilly Japan K.K., and is a consultant/advisory board member for AstraZeneca. N. Nogami reports receiving speakers bureau honoraria from Pfizer Inc., Chugai Pharmaceutical Co., Eli Lilly, MSD, TAIHO Pharmaceutical, AstraZeneca, Kyowa Hakko Kirin, ONO Pharmaceutical Co., and Bristol-Myers Squibb. G. Zhang is an employee of and has ownership interests (including patents) at Roche Molecular Solution. X. Li-Sucholeiki has ownership interests (including patents) at AstraZeneca. B. Lentrichia is an employee of and has ownership interests (including patents) at AstraZeneca. S. Dearden, S. Jenkins, and M. Saggese have ownership interests (including patents) at AstraZeneca. S.S. Ramalingam is a consultant/advisory board member for AstraZeneca, Bristol-Myers Squibb, Merck, Roche, and Tesaro, and reports receiving commercial research grants from AstraZeneca, Bristol-Myers Squibb, Merck, Amgen, Tesaro, Genmab, and Advaxis. No potential conflicts of interest were disclosed by the other authors.

©2019 American Association for Cancer Research.

Figures

Figure 1.

Patient disposition. aTissue sample not available, insufficient tissue, tissue failed pathology review. bPresence of Ex19del or L858R mutation.

Figure 2.

Investigator-assessed PFS in the plasma ctDNA EGFRm-positive subgroup (A), the plasma ctDNA EGFRm-negative subgroup (B). Tick marks indicate censored patients. CI, confidence interval; ctDNA, circulating tumor DNA; EGFRm, epidermal growth factor receptor mutation; HR, hazard ratio; PFS, progression-free survival.