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C.H. Thng
Author of
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-017 - Clinical Outcomes of Patients with EGFR T790M + NSCLC on Osimertinib (ID 8802)
09:30 - 09:30 | Author(s): C.H. Thng
- Abstract
Background:
Osimertinib (AZD9291) is a third-generation EGFR TKI specific against T790M resistance mutations in patients with metastatic EGFR-mutant (EGFRm+) NSCLC after prior first-line TKI therapy. We aimed to evaluate the clinical efficacy of osimertinib in patients treated under the AZD9291 Early Access Program (EAP) at our local institution.
Method:
This retrospective study included 57 patients who were enrolled on the AZD9291 EAP between Jul 2015 and Nov 2016 after being tested T790M+ on tumor (by direct Sanger sequencing or Roche COBAS EGFR mutation test v2) and/or plasma (cfDNA) specimens (by Lung Colon Panel v2 or ARMS PCR). Of these patients, 52 were treated with osimertinib. Tumor responses were independently assessed by radiologists using RECIST 1.1 criteria. DOR, PFS and OS were estimated by Kaplan-Meier method.
Result:
The median age at diagnosis was 58 years (range: 35-76), 80.7% patients were non-smokers, 89.5% had ECOG 0-2, 96.5% had adenocarcinoma subtype and 87.8% had either EGFR exon 19/ exon 21 mutations. Median line of therapy when osimertinib was administered was third-line (range 2nd – 9th), and 30 (53%) had brain metastasis at osimertinib initiation. RR by RECIST 1.1 was 46% (95% CI 32.2 – 60.5%) (4 CR + 20 PR) with median DOR of 8.7 months. With median follow-up of 6.2 months from osimertinib initiation, median PFS was 10.3 months (95% CI 7.52 to 15.87 months). For the 52 patients treated with osimertinib, EGFR T790M mutation was tested on the following specimens: tumor-only (n=43), plasma-only (n=25), and both (n=17). In patients with paired tumor/plasma T790M testing, 4/17 had concordant results (RR 75%), while 13 patients with discordant results [T790M+ in 8 tumor-only: RR 25% (95% CI 3.2% - 65.1%) or in 5 plasma-only: RR 40% (95% CI 5.3% - 85.3%)] had overall RR 31% (95% CI 9.1% – 61.4%). ECOG status was associated with PFS by univariable analysis, with higher ECOG 2-4 associated with shorter PFS (HR=6.54, 95% CI: 2.48 to 17.26; p<0.001) than ECOG 0-1. Line of osimertinib treatment and presence of brain metastases at osimertinib initiation were not associated with clinical outcome.
Conclusion:
Osimertinib is effective in patients with advanced EGFR T790M+ NSCLC after progression on prior EGFR TKI, regardless of presence/ absence of CNS metastasis or line of therapy. Notwithstanding ongoing optimization of plasma-based assays, T790M tumor-plasma discordance in our patient cohort is likely a reflection of overall burden of T790M subclones, and may represent a potential negative predictive biomarker of response to osimertinib.
