Abstract
Epidermal growth factor receptor (egfr) tyrosine kinase inhibitors (tkis) are standard therapy for patients with advanced or metastatic non-small-cell lung cancer harbouring an EGFR mutation. Upon progression, 50%-60% develop a secondary T790M mutation. Recent trials demonstrated outcome improvement with osimertinib compared with standard platinum-based chemotherapy as second-line therapy for patients with secondary T790M mutation. To identify T790M, a biopsy of the tumour or, more recently, plasma is necessary. This retrospective study aimed to evaluate biopsy procedures and mutational analysis at 2 Canadian cancer centres. In a retrospective review of patients who were approached to enrol in the aura2, aura3, or astris studies, demographics, eligibility for rebiopsy upon progression after an egfr tki, rebiopsy methods and complications, number of rebiopsies, and incidence of the T790M mutation were collected. Of 84 patients considered for trial enrolment, 80 signed a consent. In 78 patients who underwent rebiopsy, computed tomography or ultrasonography guidance were the most common methods used. The most common biopsy sites were lung and lymph nodes. The median number of rebiopsies performed to find a T790M mutation was 2. Only 9% of patients experienced complications. Of samples obtained, 74% were adequate for testing after initial rebiopsy. A T790M mutation was found in 47 patients, of whom 44 were enrolled on a trial. After multiple rebiopsies, only 5% of samples were inadequate for molecular analysis. In the Canadian setting, the acceptance of rebiopsy on progression was high. Multiple rebiopsies were clinically feasible and could increase the yield for T790M mutation. The incidence of complications was low despite the most common site for rebiopsy being lung.
Highlights
IntroductionAn activating mutation in exon 19 or 21 of the kinase domain of the EGFR gene, first reported in 20041,2, confers sensitivity to epidermal growth factor receptor (egfr) tyrosine kinase inhibitors (tkis), including first-generation (gefitinib, erlotinib) and second-generation types (afatinib and, more recently, dacomitinib)
An activating mutation in exon 19 or 21 of the kinase domain of the EGFR gene, first reported in 20041,2, confers sensitivity to epidermal growth factor receptor tyrosine kinase inhibitors, including first-generation and second-generation types
Osimertinib was associated with superior clinical outcomes when compared with both standard platinum–pemetrexed palliative chemotherapy in patients pre-treated with an egfr tki[18] and with first-generation egfr tkis in patients with treatment-naïve EGFR mutation–positive (EGFRm+) recurrent and metastatic nsclc[19]
Summary
An activating mutation in exon 19 or 21 of the kinase domain of the EGFR gene, first reported in 20041,2, confers sensitivity to epidermal growth factor receptor (egfr) tyrosine kinase inhibitors (tkis), including first-generation (gefitinib, erlotinib) and second-generation types (afatinib and, more recently, dacomitinib). Randomized phase iii trials showed superior median progression-free survival, objective response rate, safety and tolerability, and in some instances, median overall survival for egfr tkis compared with platinum-based chemotherapy[3,4,5,6,7,8,9,10,11,12]. Osimertinib was associated with superior clinical outcomes (progression-free survival, overall response rate, and tolerability) when compared with both standard platinum–pemetrexed palliative chemotherapy in patients pre-treated with an egfr tki (aura3)[18] and with first-generation egfr tkis in patients with treatment-naïve EGFR mutation–positive (EGFRm+) recurrent and metastatic nsclc (flaura)[19]. Epidermal growth factor receptor (egfr) tyrosine kinase inhibitors (tkis) are standard therapy for patients with advanced or metastatic non-small-cell lung cancer harbouring an EGFR mutation. Recent trials demonstrated outcome improvement with osimertinib compared with standard platinum-based chemotherapy as second-line therapy for patients with secondary T790M mutation. This retrospective study aimed to evaluate biopsy procedures and mutational analysis at 2 Canadian cancer centres
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