Afatinib has demonstrated efficacy in EGFR mutation-positive (EGFRm+) NSCLC; however, resistance develops, most commonly due to the T790M mutation. Osimertinib has shown clinical activity in the treatment of T790M-positive disease following progression on a first-line tyrosine kinase inhibitor. Further information on outcomes of sequencing options is necessary to optimize treatment outcomes.
This observational study is the first to evaluate outcomes of real-world patients who sequentially received first-line afatinib followed by osimertinib. Data were retrospectively collected for patients with common EGFRm + (Del19, L858R) advanced NSCLC and who acquired T790M after first-line afatinib. Patients must have completed afatinib and started osimertinib treatment ≥10 months prior to data entry. Patients with active brain metastases were excluded. The primary outcome was time on treatment (ToT) from initiation of afatinib until discontinuation of osimertinib.
A total of 204 patients were included; of these, 24.5/67.6% were Asian and non-Asian (Caucasian and African American), 15.3% had ECOG performance status ≥2, and 73.5/26.0% were Del19/L858R-positive. Overall median ToT 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%. ToT was generally consistent across patient subgroups; however, ToT was longer in Asian patients (n = 50; median 46.7 months; 90% CI: 26.8–not reached) and in those with Del19-positive disease (n = 150; median 30.3 months; 90% CI: 27.6–44.5). Patients with poor prognosis, such as those with ECOG PS ≥ 2 (n = 31, median ToT 22.2 months; 90% CI: 16.0–27.0) and stable brain metastases (n = 21, median ToT 19.4 months; 90% CI: 16.0–not reached), also appeared to derive clinical benefit. 6.6% of patients developed brain metastases on afatinib therapy.
In real-world clinical practice, sequential afatinib and osimertinib facilitates prolonged, chemotherapy-free treatment in patients with T790M-acquired resistance, and may be an attractive strategy, especially for Del19-positive tumors.
Jane Saunders of GeoMed, an Ashfield company, part of UDG Healthcare plc.
NCT03370770.
Boehringer Ingelheim.
Boehringer Ingelheim.
M.J. Hochmair: Advisory council or committee: Böhringer Ingelheim, AstraZeneca, Pfizer, MSD, Roche A. Morabito: Honoraria: Boehringer Ingelheim, Roche, AstraZeneca, Pfizer, MSD, Bristol Myers Squibb. D. Hao: Research funding and consultancy: Boehringer Ingelheim and AstraZeneca. R.A. Soo: Grants and personal fees: AstraZeneca; Personal fees: BMS, Boehringer Ingelheim, Celgene, Lilly, Merck, Novartis, Pfizer, Roche, Taiho, Ignyta. J.C-H. Yang: Personal fees: BI, Eli Lilly, Roche/Genentech, Chugai, Astellas, MSD, Merck Serono, Pfizer, Novartis, Celgene, Merrimack, Yuhan Pharmaceuticals, BMS, Ono Pharmaceuticals, Daiichi Sankyo, AstraZeneca, Hansoh Pharmaceuticals, Takeda Pharmaceuticals. B. Halmos: Grants and personal fees: Boehringer Ingelheim, AstraZeneca, Pfizer, Novartis, Takeda, Personal fees: Genentech/Roche, Grants: Merck. L. Wang, A. Golembesky, A. Märten: Employed by Boehringer Ingelheim. T. Cufer: Consultancy and honoraria: AstraZeneca, Roche, Pfizer, MSD, Bristol Myers Squibb, Boehringer Ingelheim. All other authors have declared no conflicts of interest.