Osimertinib, an oral, irreversible EGFR-TKI selective for sensitising (EGFRm) and T790M resistance mutations, has been shown to be effective and well tolerated in clinical studies for pts with EGFR T790M positive aNSCLC. Pts in France had early access to osimertinib through an ATU program before approval.
Pts with EGFR T790M positive aNSCLC were eligible if they had received prior EGFR-TKI therapy and a platinum-based chemotherapy (CT) or had CT intolerance; additional lines of therapy were permitted. T790M testing was performed by INCA (French National Cancer Institute) certified platforms.
From 07/04/2015 to 24/03/2016, 134 centres enrolled 364 pts; 99% had stage IV adenocarcinoma and 38.5% had brain metastases. Median therapies prior to osimertinib was 2 (1–9). The most frequent prior therapies were 1st line EGFR-TKI (66.2%; median duration 15.2 mo) and 2nd line platinum-based CT (42.0%).
|N = 364|
|Age, years Median (range)||68 (28–92)|
|Sex, % Male/female||32.9/67.1|
|Smoking status, % Never/former/current||77.5/19.6/1.8|
|Performance status, % 0-1/ ≥ 2||82.6/17.4|
|EGFR mutation at diagnosis, %|
|De novo T790M/Other||10.5/4.8|
|T790M testing material post EGFR-TKI relapse, %|
|Including primary and/or metastasis + plasma||2.7|
|Pleural fluid + plasma||0.6|
|Osimertinib therapy line, % 2/3/ ≥ 4||22.5/38.2/39.3|
As of March 2016, 350 pts were treated, 14 excluded (prescriber decision / pt death). 61% were treated ≥3 mo, 30% ≥6 mo and 14% ≥9 mo. Overall response rate (ORR) in 123 pts evaluable was 61.8% (95% CI 53, 70) (CR 5.7%, PR 56.1%). Disease control rate (CR + PR + SD) was 80.5% (99/123). 309/350 pts (88.3%) ongoing at data cutoff, 23 pts withdrawn for disease progression. Investigator reported safety data (n = 350) showed 36 pts (10.3%) experienced ≥1 treatment-related AE, 13 pts (3.7%) had AEs leading to discontinuation. 12 pts (3.4%) died (1 death drug related, attributed by investigator). 9 pts (2.6%) had AEs resulting in dose reductions; 3 pts (0.9%) had temporary interruptions.
In pts with EGFR T790M positive aNSCLC, osimertinib had antitumour activity with a similar ORR to that in clinical studies, with good tolerability. Identification of eligible pts is feasible in daily practice at tumour progression by T790M testing on rebiopsy or using ctDNA.
Clinical trial identification
NL 46006-46007 September 2015
Legal entity responsible for the study
D. Planchard: Personal fees from AstraZenaca, Boehringer, Clovis, Novartis, Sanofi aventis, BMS, Roche, Lilly, Pfizer, and grants from Novartis. M. Pérol: Personal fees from Astra-Zeneca, Clovis Oncology, Roche, Boehringer-Ingelhaim, outside the submitted work. A. Cortot: Personal fees from Astrazeneca. J. Cadranel: Personal fees from BI, Roche, AstraZeneca. R. Schott: Personal fees from Roche SAS and Pierre Fabre; and non-financial support from Roche SAS, Pierre Fabre, Novartis, Astra Zeneca, Lilly, and Amgen. E. Dansin: Personal fees from AstraZeneca, Roche and Clovis. D. Moro-Sibilot: Personal fees from Astrazeneca, Pfizer, Novartis, Clover, El Lilly, Roche, and Ariad. J-C. Soria: Personal fees from AstraZeneca, Pfizer, Pierre fabre, Roche, Sanofi, and Servier. M. Coudurier: Personal fees and non-financial support from Aztra Zeneca, Roche, BI, Clovis, during the study; grants, personal fees and non-financial support from Msd, BMS, Roche, Lilly, BI, Amgen, outside the submitted work. A. Gourion: Personal fees from AstraZeneca, during the conduct of the study. N. Varoqueaux: Other from AstraZeneca, during the conduct of the study. C. Chouaid: Grants, personal fees and nonfinancial support from Aztra Zeneca, Roche, BI, Clovis, during the conduct of the study; grants, personal fees and nonfinancial support from MSD, BMS, Roche, Lilly, BI, Amgen, outside the study. All other authors have declared no conflicts of interest.