Abstract 4002
Background
Afatinib is effective in EGFRm+ NSCLC; however, resistance develops over time, most commonly due to emergence of the T790M mutation. Osimertinib has shown efficacy in the treatment of T790M-positive NSCLC after progression on a first-line TKI. Further information on sequencing outcomes is needed to optimize treatment outcomes.
Methods
This observational study is the first to evaluate real-world outcomes of sequential afatinib followed by osimertinib. Data were retrospectively collected from patients with EGFRm + (Del19, L858R) advanced NSCLC and acquired T790M after first-line afatinib. Patients must have completed afatinib and started osimertinib ≥10 months prior to enrollment. Those with active brain metastases were excluded. The primary outcome was time to treatment failure (TTF) from initiation of afatinib until discontinuation of osimertinib.
Results
204 patients were included; 24.5/67.6% were Asian/non-Asian, 73.5/26.0% were Del19/L858R+, and 83.7% started on afatinib 40 mg. The study included patients with poor prognosis features who are often excluded from clinical trials; 31 (15.2%) patients had ECOG PS ≥ 2 and 21 (10.3%) had stable brain metastases. As of May 2018, overall median TTF was 27.6 months (90% CI: 25.9, 31.3). Median time on afatinib and osimertinib was 11.9 months (90% CI: 10.9, 12.2) and 14.3 months (90% CI: 12.8, 15.9), respectively. The 2-year OS rate was 78.9%. TTF was generally consistent across subgroups, but was longer in Asian patients (n = 50; median 46.7 months; 90% CI: 26.8, NR) and those with Del19+ disease (n = 150; median 30.3 months; 90% CI: 27.6, 44.5). Results were similar in patients who started on the approved 40mg dose of afatinib; median TTF was 27.6 months (90% CI: 26.3, 31.3) overall and 46.7 months (90% CI: 36.4, 46.7) in Asian Del19+ patients. OS and updated TTF data will be presented.
Conclusions
First-line afatinib followed by osimertinib is feasible in a broad, real-world patient population with EGFRm+ NSCLC and acquired T790M mutation. The benefit of sequential afatinib followed by osimertinib was observed across all patient subgroups, particularly in those with Del19+ disease and Asian patients.
Clinical trial identification
NCT03370770.
Editorial acknowledgement
Fiona Scott of GeoMed, an Ashfield company, part of UDG Healthcare plc; funded by Boehringer Ingelheim.
Legal entity responsible for the study
Boehringer Ingelheim.
Funding
Boehringer Ingelheim.
Disclosure
M.J. Hochmair: Honoraria (self): AstraZeneca; Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Merck Sharp & Dohme; Honoraria (self): Pfizer; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self): Novartis. A. Morabito: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Merck Sharp & Dohme. D. Hao: Advisory / Consultancy, Research grant / Funding (self), Research funding/consultancy: Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (self), Research funding/consultancy: AstraZeneca. R. Soo: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): AZ; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): BI; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Ignyta; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Taiho; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: Yuhan. J.C. Yang: Honoraria (self): BI; Honoraria (self): Eli Lilly; Honoraria (self): Bayer; Honoraria (self): Roche/Genentech; Honoraria (self): Chugai; Honoraria (self): MSD; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): BMS; Honoraria (self): Ono Pharma; Advisory / Consultancy: Astellas; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Celgene; Advisory / Consultancy: Merrimack; Advisory / Consultancy: Yuhan Pharma; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: Hansoh Pharma; Advisory / Consultancy: Takeda Pharma; Advisory / Consultancy: Blueprint Medicines; Advisory / Consultancy: G1 Therapeutics. B. Halmos: Advisory / Consultancy, Research grant / Funding (self): AZ; Advisory / Consultancy, Research grant / Funding (self): Pfizer; Advisory / Consultancy, Research grant / Funding (self): Novartis; Advisory / Consultancy, Research grant / Funding (self): Merck; Advisory / Consultancy, Research grant / Funding (self): BMS; Advisory / Consultancy, Research grant / Funding (self): BI; Advisory / Consultancy: Genentech; Advisory / Consultancy: Spectrum; Advisory / Consultancy: Ignyta; Advisory / Consultancy, Research grant / Funding (self): Guardant Health; Research grant / Funding (self): Mirati; Research grant / Funding (self): AbbVie; Research grant / Funding (self): GSK; Advisory / Consultancy: Foundation Medicine. L. Wang: Full / Part-time employment: Boehringer Ingelheim. A. Golembesky: Full / Part-time employment: Boehringer Ingelheim. A. Märten: Full / Part-time employment: Boehringer Ingelheim. T. Cufer: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim. All other authors have declared no conflicts of interest.
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