Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study

Cell free DNA analysis by SiRe® next generation sequencing panel in non small cell lung cancer patients: focus on basal setting

“…In particular, we detected 22% KRAS, 6% NRAS and 3% BRAF mutated samples, with only one patient that showed two concurrent mutations (NRAS p.G13D and KRAS p.Q61H). It is remarkable to note that the mutation distribution in cfDNA of this NSCLC baseline patient series was very similar to that reported on tissues derived DNA by previous studies exploiting a multi-gene assay in NSCLC (18)(19)(20)(21).…”

“…SiRe ® , with a lower limit of detection of 0.01% and a reference range of 568 clinical relevant mutations, showed a higher analytical performance respect to a very sensitive modified TaqMan probe real time PCR based approach (13). In the clinical trials settings and in other published validation studies (18)(19)(20), the analysis of cfDNA gene mutations was carried out using as gold standard the mutational status obtained on matched tissue derived DNA, but little is known regarding the application of this approach in clinical setting, in particular in baseline setting of NSCLC patients, prior to EGFR TKIs administration, without a referent DNA derived tissue to confirm the mutational data obtained on cfDNA (21).…”

Optimizing outcomes in EGFR Mutation-Positive Nsclc: Which Tyrosine Kinase Inhibitor and When?

“…These results were confirmed in the Phase II AURA extension, in patients with EGFR TKI-pretreated EGFR T790M-positive disease, where the response rate was reported as 62% and median PFS was 12.3 months [7]. Similarly, in the AURA2 study in patients who had progression on previous EGFR TKI therapy, the response rate was 70% [37]. Pooled OS analysis from AURA2 and the AURA extension showed median OS of 26.8 months from initiation of osimertinib in patients with T790M-positive NSCLC that had progressed after a first-or second-line EGFR TKI [38].…”

Raising the bar: the future of EGFR inhibition in non-small lung cancer

“…As a mutantselective, covalent inhibitor of the acquired EGFR T790M resistance mutation, osimertinib is currently an approved second-line therapy for EGFR patients who develop resistance to first-line EGFR TKIs mediated by the T790M mutation. Previously reported cohorts from the AURA study have shown overall response rates for patients with T790M-mediated acquired resistance ranging from 62-70% with a median PFS ranging from 9.9-12.3 months (8,9). Moreover, when compared to platinum chemotherapy, osimertinib is markedly more effective in this patient cohort, with an ORR of 71% vs. 31%, respectively (10).…”