Acquisition of Epidermal Growth Factor Receptor mutation (EGFRm) resistance (mainly T790M) to EGFR tyrosine kinase inhibitors (TKI) occurs in about half of NSCLC patients (pts) treated with TKI. Mutational status is important to guide next therapy. The aim of this study was to analyse the value of liquid and tissue rebiopsy for evaluation of EGFR mutational status, in a real-world setting.
Retrospective review of medical charts of pts with advanced EGFRm NSCLC treated at a Portuguese cancer center between January 2015 and October 2019.
Of 824 patients evaluated for EGFRm, 160 (19%) had EGFRm positive NSCLC. Eighty-five of 160 pts (53%) had advanced disease. Median age at diagnosis was 69 years old [range: 39-95] and 66% were female. History of tobacco use was reported in 42%. Sixty-nine of 85 pts (81%) received TKI and all the 46 pts (67%) who developed disease progression (DP) on TKI were submitted to a first (1st) rebiopsy: 25 liquid biopsies (LB) and 25 tissue biopsies/citologies (CTB). Among those, 16 pts (35%) underwent a 1st rebiopsy that harbored a T790M mutation. Among the 30 remaining pts, 12 did not repeat biopsy and 18 were submitted to a second and third (2nd/3rd) rebiopsy. Five of those 18 pts (28%) harbored a T790M mutation. In all 18 pts with exclusive intrathoracic disease, LB failed to identify T790M mutation, regardless of the number of rebiopsies. Out of those 20 negative LB, one had a positive matched CTB. But regarding CTB, T790M mutation was identified in 5 of 20 CTB (25%). Among 28 pts with extrathoracic disease, T790M mutation was detected in 17 out of 44 rebiopsies perfomed (39%): 10 out of 30 LB (33%) and in 7 out of 14 CTB (50%).
Our results suggest that 2nd/3rd rebiopsies are worth performing, as the proportion of pts with mutation identified is still significant and have a clinical impact in therapeutic choices and prognosis. T790M mutation is less identified in pts with exclusive intrathoracic disease. LB might not add value in this setting but CTB must be considered. In extrathoracic disease, a higher proportion of T90M mutation was identified both in CTB and LB. Although CTB was better than LB, it is more difficult to perform and more invasive. Prospective studies are needed to validate these findings.
Clinical trial identification
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All authors have declared no conflicts of interest.