Epidermal growth factor receptor mutation analysis in tissue and plasma from the AURA3 trial: Osimertinib versus platinum‐pemetrexed for T790M mutation‐positive advanced non–small cell lung cancer
Background This study assesses different technologies for detecting epidermal growth factor receptor (EGFR) mutations from circulating tumor DNA in patients with EGFR T790M‐positive advanced non–small cell lung cancer (NSCLC) from the AURA3 study (NCT02151981), and it evaluates clinical responses to...
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Published in | Cancer Vol. 126; no. 2; pp. 373 - 380 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Wiley Subscription Services, Inc
15.01.2020
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Subjects | |
Online Access | Get full text |
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Summary: | Background
This study assesses different technologies for detecting epidermal growth factor receptor (EGFR) mutations from circulating tumor DNA in patients with EGFR T790M‐positive advanced non–small cell lung cancer (NSCLC) from the AURA3 study (NCT02151981), and it evaluates clinical responses to osimertinib and platinum‐pemetrexed according to the plasma T790M status.
Methods
Tumor tissue biopsy samples were tested for T790M during screening with the cobas EGFR Mutation Test (cobas tissue). Plasma samples were collected at screening and at the baseline and were retrospectively analyzed for EGFR mutations with the cobas EGFR Mutation Test v2 (cobas plasma), droplet digital polymerase chain reaction (ddPCR; Biodesix), and next‐generation sequencing (NGS; Guardant360, Guardant Health).
Results
With cobas tissue test results as a reference, the plasma T790M positive percent agreement (PPA) was 51% (110 of 215 samples) by cobas plasma, 58% (110 of 189) by ddPCR, and 66% (136 of 207) by NGS. Plasma T790M detection was associated with a larger median baseline tumor size (56 mm for T790M‐positive vs 39 mm for T790M‐negative; P < .0001) and the presence of extrathoracic disease (58% for M1b‐positive vs 39% for M0‐1a‐positive; P = .002). Progression‐free survival (PFS) was prolonged in randomized patients (tissue T790M‐positive) with a T790M‐negative cobas plasma result in comparison with those with a T790M‐positive plasma result in both osimertinib (median, 12.5 vs 8.3 months) and platinum‐pemetrexed groups (median, 5.6 vs 4.2 months).
Conclusions
PPA was similar between ddPCR and NGS assays; both were more sensitive than cobas plasma. All 3 test platforms are suitable for routine clinical practice. In patients with tissue T790M‐positive NSCLC, an absence of detectable plasma T790M at the baseline is associated with longer PFS, which may be attributed to a lower disease burden.
This exploratory analysis of the AURA3 study demonstrates that plasma‐based platforms (cobas EGFR Mutation Test v2, next‐generation sequencing, and droplet digital polymerase chain reaction) are suitable for epidermal growth factor receptor mutation detection in routine clinical practice. In patients with tissue T790M‐positive non–small cell lung cancer, the absence of detectable plasma T790M is associated with longer progression‐free survival, which may be attributed to a lower disease burden. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 ObjectType-News-3 content type line 23 |
ISSN: | 0008-543X 1097-0142 |
DOI: | 10.1002/cncr.32503 |