Background:Osimertinib is a potent, oral, irreversible EGFR-TKI with efficacy in pts with EGFR-TKI sensitising (EGFRm) and T790M mutation positive advanced NSCLC. We present updated data from a P1 dose expansion cohort (AURA P1, NCT01802632) and a pre-planned pooled analysis of two P2 studies (AURA extension, NCT01802632 and AURA2, NCT02094261) that investigated osimertinib at the recommended 80 mg daily dose. Methods: Pts with EGFRm and T790M-positive advanced NSCLC who had progressed following EGFR-TKI therapy received osimertinib 80 mg once daily. T790M-positive status was confirmed via central testing of biopsy samples (cobas ® EGFR Mutation Test). Pts had measurable disease, WHO performance status 0/1 and acceptable organ function; stable brain metastases were allowed. Objective response rate (ORR) was the primary endpoint; duration of response (DoR) and progression-free survival (PFS) were secondary endpoints. Results: Results are from a 4 Jan 2016 data cut-off for AURA P1 80 mg treated T790M positive population and 1 Nov 2015 for AURA pooled P2. A total of 63 pts and 411 pts were assigned to treatment in AURA P1 (80 mg T790M positive population only) and AURA pooled P2, respectively. In AURA P1,
noninferiority phase 3 trial, we enrolled patients with advanced NSCLC previously treated with cytotoxic chemotherapy. Patients were randomly allocated (1:1) to receive docetaxel (60 mg/m 2 ) on day 1 or nab-paclitaxel (100 mg/m 2 ) on days 1, 8, and 15 of a 21-day cycle. The primary end point was overall survival analyzed on an intention-totreat basis. Adverse events were assessed according to treatment received. Results: Between 22 May 2015 and 12 March 2018, 503 patients were randomly allocated to treatment. Median overall survival was 13.6 months (95% CI, 10.9e16.5) for the 251 patients allocated to docetaxel and 16.2 months (95% CI, 14.4e19.0) for the 252 patients allocated to nab-paclitaxel (hazard ratio, 0.85; 95.2% CI, 0.68e1.07). Median progression-free survival was 4.2 months (95% CI, 3.9e5.0) for the nab-paclitaxel group versus 3.4 months (95% CI, 2.9e4.1) for the docetaxel group (hazard ratio, 0.76; 95% CI, 0.63e0.92; p¼0.0042). The objective response rate was 29.9% (95% CI, 24.0e36.2) for the nab-paclitaxel group and 15.4% (95% CI, 10.9e20.7) for the docetaxel group (p¼0.0002), and it showed a significant improvement for nabpaclitaxel versus docetaxel regardless of tumor histology. Adverse events of grade !3 included febrile neutropenia (55 [22%] of 249 patients in the docetaxel group versus 5 [2%] of 245 patients in the nab-paclitaxel group) and peripheral sensory neuropathy (2 [1%] versus 24 [10%], respectively). Conclusion: The trial showed that nabpaclitaxel was noninferior to docetaxel in terms of overall survival. Nab-paclitaxel should thus be considered a standard treatment option for previously treated patients with advanced NSCLC.
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