奥西默替尼
T790米
医学
内科学
基因分型
胃肠病学
肿瘤科
光环
无进展生存期
表皮生长因子受体
化疗
基因型
癌症
吉非替尼
埃罗替尼
遗传学
基因
生物
偏头痛
作者
Kenneth S. Thress,Aleksandra Markovets,J. Carl Barrett,Juliann Chmielecki,Sarah B. Goldberg,Frances A. Shepherd,Sarah L. Vowler,Geoffrey R. Oxnard
标识
DOI:10.1200/jco.2017.35.15_suppl.9018
摘要
9018 Background: Osimertinib, an EGFR T790M-selective tyrosine kinase inhibitor (TKI), provides high and durable response rates in patients (pts) with T790M positive advanced NSCLC whose disease has progressed following EGFR-TKI therapy. We investigated whether changes in the levels of plasma EGFRmutations post-osimertinib treatment are associated with clinical outcome. Methods: We studied pts from the AURA Phase I study (NCT01802632) with acquired resistance to EGFR-TKIs, T790M positive baseline genotyping (in tumor or plasma), and plasma samples collected at baseline and 6 weeks (wks) post- osimertinib (20–240 mg daily) treatment. Plasma samples were analyzed for the presence of detectable EGFR mutations (Ex19del, L858R and T790M) using BEAMing digital PCR (Sysmex/Inostics). In pts with detectable plasma EGFR mutations at baseline, clinical outcomes (by investigator, per RECIST 1.1) were compared for pts with or without detectable plasma EGFRmutations at 6 wks. Results: Evaluable baseline and 6 wk plasma samples were collected from 160 pts with T790M positive genotyping, of whom 143 had detectable EGFR mutations at baseline (median allelic fraction for Ex19del: 7.09%; L858R: 3.81%; T790M: 2.12%). In this cohort, the overall median progression-free survival (mPFS) was 9.3 months (m; 95% CI 8.2, 9.7). Clearance of plasma EGFRmutations at 6 wks was seen in 92/143 (64%) pts. mPFS was longer in pts with plasma clearance (10.9 m; 95% CI 9.5, 15.2) compared with pts without (5.5 m; 95% CI 3.9, 6.7), as was objective response rate (ORR; 70%; 95% CI 59%, 79% vs. 35%; 95% CI 22%, 50%). Conclusions: Clearance of plasma EGFR mutations after 6 wks of osimertinib therapy appears to be associated with improved ORR and mPFS in pts with T790M positive NSCLC. Evidence or lack of such a “plasma response” measured at 6 wks could, potentially, be used to predict subsequent outcomes on therapy. Further research is needed to better understand whether continued detection of plasma EGFR mutations at 6 wks may indicate the presence of heterogeneous resistance mechanisms, which could, potentially, be targeted by combination therapies. Validation of these results in an independent cohort of pts is ongoing. Clinical trial information: NCT02228369.
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