EGFR tyrosine kinase inhibitors (EGFR-TKIs) are standard therapy for EGFRm aNSCLC. Upon progression, 50-60% will develop the secondary T790M mutation. Recent trials demonstrated improvement in outcomes with osimertinib over standard platinum-based chemotherapy as 2L therapy for T790M-positive EGFRm aNSCLC. To identify T790M, tumour biopsy or plasma testing is necessary. This study aimed to evaluate biopsy procedures and mutational analysis at two Canadian cancer centres.
BC Cancer-Vancouver and Cross Cancer Institute performed a retrospective review of pts who signed consent to enroll to the AURA2, AURA3 or ASTRIS studies. Pt characteristics, biopsy method, rebiopsy methods/complications, number of rebiopsies performed, and incidence of the T790M mutation were collected.
84 pts were considered for trial enrolment. 80 signed consent with M:F 32:68%; ECOG 0/1/2: 11/66/23%; smoker/ex-smoker/never smoker: 6/21/73%; exon 19/L858R/other: 60/36/4%; prior curative intent treatment in 18%. 78 pts underwent biopsy, most commonly CT/US-guided biopsy (50%), bronchoscope/EBUS (32%), thoracentesis/surgical biopsy (12%). 3 pts had plasma testing. Type of biopsies were cores (47%), fine needle biopsy (18%), transbronchial biopsy (14%), other (21%). The most common sites for biopsy were lung or nodes (64%). The median number of biopsies performed was 2. Only 8% of pts experienced complications after biopsy. 77% of samples were adequate for T790M testing: 35% performed locally, 65% centrally. Overall, 47 pts were found to have T790M; of which, 44 were enrolled in a trial. Among 40 pts who were ineligible for trials, reasons included: T790M negative (72.5%), decline in performance status/death (15%), inadequate tissue (5%), biopsy refusal, unable to biopsy, and symptomatic brain metastases requiring radiation (2.5% each). Additional data on practice pattern will be presented.
Patients and physicians were amenable to re-biopsy at progression for further tumor characterization and treatment selection. The incidence of complications was low despite the majority being pulmonary biopsies. 23% of the samples were not adequate for molecular analysis.
Clinical trial identification
Legal entity responsible for the study
University of Alberta, Alberta Health Services, Cross Cancer Institute and AstraZeneca.
Q.S-C. Chu: Honorarium: AstraZeneca, BMS, BI, Eisai, Lily, Merck, Novartis, Roche, Takeda; Research funding: AstraZeneca. N.C. Devost, R. Walton: Employee: AstraZeneca. C. Ho: Honorarium and research funding: AstraZeneca. All other authors have declared no conflicts of interest.