Osimertinib is an oral, potent, CNS active, irreversible EGFR-TKI approved to treat pts with T790M-positive advanced NSCLC. Here we present updated data from a pre-planned pooled analysis of Phase II studies: AURA extension (NCT01802632), AURA2 (NCT02094261).
Pts with centrally confirmed T790M-positive (by cobas® EGFR Mutation Test) advanced NSCLC, who had progressed following EGFR-TKI treatment, received osimertinib 80 mg once daily. Other inclusion criteria were measurable disease, WHO performance status 0/1 and acceptable organ function. Pts with stable CNS metastases were eligible. The primary efficacy endpoint was objective response rate (ORR) by RECIST 1.1 per blinded independent central review (BICR). Secondary endpoints included duration of response (DoR), progression-free survival (PFS), OS and safety.
As of the 1 Nov 2016 data cut-off (DCO) 411 pts had received osimertinib (129 pts as second-line and 282 pts as ≥third-line); median treatment exposure was 16.4 months (mo; range 0–29.7 mo). Pooled results (BICR) were: ORR (evaluable for response set; EFR), 66% (95% confidence interval [CI] 61, 70); median DoR (EFR), 12.3 mo (95% CI 11.1, 13.8); median PFS (full analysis set), 9.9 mo (95% CI 9.5, 12.3). At DCO, 188 pts (46%) had died, 191 pts (47%) remained in survival follow up, and 32 pts (8%) had discontinued before death. Pooled median OS was 26.8 mo (95% CI 24.2, not calculable [NC]); median OS in the second-line and ≥third-line cohorts (95% CI) was 25.8 mo (24.0, NC) and NC (22.1, NC), respectively. The 12 and 24 mo survival rates were 80% and 56%, respectively. The most common (investigator assessed) possibly causally-related adverse events (AEs) were rash (grouped term 42%, [grade ≥3, 1%]) and diarrhoea (39% [
With a median treatment exposure of 16.4 mo, osimertinib resulted in a median OS of 26.8 mo. This pooled analysis represents the most mature clinical trial data for osimertinib in pts with pre-treated T790M positive advanced NSCLC, and further establishes osimertinib as standard of care in this setting.
Clinical trial identification
AURA extension (NCT01802632), AURA2 (NCT02094261)
Legal entity responsible for the study
T. Mitsudomi: Honoraria: AstraZeneca, Boehringer- Ingelheim, Chugai Research grant: Boehringer-Ingelheim, Chugai. L. Bazhenova: Advisory board: AstraZeneca. F. Blackhall: Honoraria: AstraZeneca, Pfizer, Boehringer Ingelheim, Medivation, Novartis, MSD, BMS Consulting/Advisory role: Medivation, Roche. Research funding: AstraZeneca, Pfizer, Boehringer Ingelheim, Medivation, Novartis, MSD, BMS. Expense: Boehringer Ingelheim. T. Hida: Research funding and honoraria: Chugai Pharmaceutical, Novartis Pharma, Taiho Pharmaceutical, AstraZeneca, Nippon Boehringer Ingelheim, Clovis Oncology, Astellas. M. Majem Tarruella: Advisory Board: Novartis, Roche, Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim. S.L. Vowler, G. Laus: Employee of AstraZeneca. P.A. Jänne: AstraZeneca – consulting and sponsored research Boehringer Ingelheim – consulting Pfizer – consulting Roche/Genentech – consulting Chugai Pharmaceuticals – consulting ARIAD – consulting Astellas – sponsored research. J.C-H. Yang: Honorarium/Ad board: Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech/Chugai, Astellas, MSD, Merck Serono, Pfizer, Novartis, Clovis Oncology, Celgene, Merrimack, Yuhan Pharma, BMS, Ono pharma Daiichi Sankyo, AstraZeneca, Hansoh Pharmaceuticals. All other authors have declared no conflicts of interest.