OA03 Afatinib Followed by Osimertinib in Real-World Patients with EGFR Mutation-Positive Advanced NSCLC: The Giotag Study

Afatinib has demonstrated efficacy in EGFR mutation-positive (EGFRm+) NSCLC; however, resistance develops over time, most commonly due to the emergence of 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 for patients. 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 between December 2017 and May 2018. Patients had common EGFRm+ (Del19, L858R) advanced NSCLC and acquired T790M after first-line afatinib. Patients must have completed afatinib treatment 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 in the study; 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. First-line afatinib followed by osimertinib is a feasible therapeutic strategy in a broad, real-world patient population with EGFRm+ NSCLC and acquired T790M mutation, resulting in 27.6 months of chemotherapy-free treatment. The benefit of sequential afatinib followed by osimertinib was observed across patient subgroups, with prolonged benefit seen in some subgroups, including those with Del19-positive disease.