Second- (afatinib and dacomitinib) and third-generation (osimertinib) EGFR tyrosine kinase inhibitors (TKIs) have demonstrated superior efficacy versus the first-generation EGFR TKIs (erlotinib and gefitinib) for EGFRm+ NSCLC. However, TKI resistance is inevitable and up to 75% of afatinib-treated patients develop the T790M mutation. Hence, questions remain about the optimal sequence of EGFR TKIs. The observational GioTag study investigated outcomes in patients with EGFRm+ NSCLC treated with sequential afatinib and osimertinib in a ‘real-world’ setting. Time to treatment failure (TTF) and overall survival (OS) were encouraging (Hochmair et al Future Oncol 2019). Here, we report final TTF and OS data for Asian patients.
Data were retrospectively collected for patients with EGFRm+ (Del19, L858R) NSCLC who had T790M+ disease after first-line afatinib and then received osimertinib. TTF was the primary outcome; OS analysis was exploratory.
203 patients were included in the global GioTag study; of these, 50 were Asian. After a median follow-up of 33.9 months, median TTF was 37.1 months (90% CI: 28.1–40.3) and median OS was 44.8 months (90% CI: 37.0–57.8) in Asian patients (overall global study population: median TTF 27.7 months [90% CI: 26.7–29.9], median OS 37.6 months [90% CI: 35.5–41.3]). Clinical benefit was particularly encouraging in Asian patients with Del19-positive disease (n=31): median TTF 40.0 months (90% CI: 36.4–45.0), median OS 45.7 months (90% CI: 38.2–57.8). Median TTF and OS were 38.2 months (90%: 28.9–40.3) and 44.8 months (90% CI: 38.2–57.8), respectively, in Asian patients who received a starting dose of afatinib 40 mg (n=46), and 36.4 months (90% CI: 28.1–41.7) and 41.3 months (90% CI: 36.9–57.8), respectively, in Asian patients with ECOG performance status 0/1 (n=45).
In a real-world clinical practice setting, sequential afatinib and osimertinib is effective, particularly in Asian patients with EGFRm+ NSCLC who develop T790M. Median OS was nearly 4 years in those with Del19+ disease, suggesting sequential TKI use could potentially allow these patients to receive long-term chemotherapy-free treatment.
NCT03370770.
Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Jane Saunders, of GeoMed, an Ashfield company, part of UDG Healthcare plc.
Boehringer Ingelheim.
Boehringer Ingelheim.
M.J. Hochmair: Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda. A. Morabito: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Takeda; Honoraria (self): BMS; Honoraria (self): MSD. D. Hao: Advisory/Consultancy: Roche; Honoraria (self), Research grant/Funding (self): AstraZeneca; Research grant/Funding (self), Travel/Accommodation/Expenses: Boehringer Ingelheim. C-T. Yang: Advisory/Consultancy: BI; Advisory/Consultancy: MSD; Advisory/Consultancy: Ono; Advisory/Consultancy: Chugai; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Pfizer. R.A. Soo: Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self), Research grant/Funding (self): Boehringer Ingelheim; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Eli Lilly; Honoraria (self): Merck; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): Taiho; Honoraria (self): Takeda; Honoraria (self): Yuhan; Honoraria (self): Amgen. J.C-H. Yang: Honoraria (institution), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (institution), Advisory/Consultancy: AstraZeneca; Honoraria (institution), Advisory/Consultancy: Roche/Genentech; Honoraria (institution), Advisory/Consultancy: Lilly; Honoraria (institution), Advisory/Consultancy: MSD Oncology; Honoraria (institution), Advisory/Consultancy: Merck Sernono; Honoraria (institution), Advisory/Consultancy: Celgene; Honoraria (institution), Advisory/Consultancy: Bayer; Honoraria (institution), Advisory/Consultancy: Pfizer; Honoraria (institution), Advisory/Consultancy: Ono Pharmaceutical; Honoraria (institution), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (institution), Advisory/Consultancy: Yuhan; Honoraria (institution), Advisory/Consultancy: Hansoh; Honoraria (institution), Advisory/Consultancy: Brueprint Medicines; Honoraria (institution), Advisory/Consultancy: Daiichi Snakyo; Honoraria (institution), Advisory/Consultancy: Amgen; Honoraria (institution), Advisory/Consultancy: Takeda Oncology; Honoraria (institution), Advisory/Consultancy: Incyte; Honoraria (institution), Advisory/Consultancy: Boehringer Ingelheim; Roche; MSD; AstraZeneca; Novartis; Bristol-Myers Squibb; Ono Pharmaceutical; Takeda Oncology; Eli Lilly; Pfizer. B. Halmos: Advisory/Consultancy, Research grant/Funding (self): Merck; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy, Research grant/Funding (self): Pfizer; Advisory/Consultancy, Research grant/Funding (self): Astra-Zeneca; Advisory/Consultancy, Research grant/Funding (self): Boehringer Ingelheim; Advisory/Consultancy: Spectrum; Advisory/Consultancy, Research grant/Funding (self): Takeda; Advisory/Consultancy, Research grant/Funding (self): BMS; Advisory/Consultancy, Research grant/Funding (self): Amgen; Advisory/Consultancy, Research grant/Funding (self): Guardant Health; Advisory/Consultancy: Foundation One; Advisory/Consultancy: TPT; Research grant/Funding (self): Eli-Lilly; Research grant/Funding (self): GSK; Research grant/Funding (self): Mirati; Research grant/Funding (self): AbbVie. A. Märten: Full/Part-time employment: Boehringer Ingelheim. T. Cufer: Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda. All other authors have declared no conflicts of interest.