PD2.05 Overall Survival in Pts with EGFRm+ NSCLC Receiving Sequential Afatinib and Osimertinib: Updated Analysis of the GioTag Study

Abstract

While the superiority of second- and third-generation EGFR tyrosine kinase inhibitors (TKIs) over first-generation agents has been clearly demonstrated, the optimal sequence of EGFR TKIs is less clear, especially as there is no established targeted therapy after osimertinib failure. In the observational GioTag study (NCT03370770), patients with EGFRm+ NSCLC were treated with sequential afatinib and osimertinib in a ‘real-world’ clinical setting, including patients with poor prognosis (ECOG PS ≥2: 15%; stable brain metastases: 10%).1 Encouraging time to treatment failure (TTF) was seen in the primary analysis (overall: 27.6 months; Del19-positive patients: 30.3 months; Asian patients: 46.7 months). In this analysis, we report OS and updated TTF. Data were retrospectively collected between Dec 2017 and June 2018 for 204 patients with EGFRm+ (Del19, L858R) NSCLC who were T790M-positive after first-line afatinib and received subsequent osimertinib. TTF was the primary outcome; OS analysis was exploratory. Data were collected from electronic health records (EHRs; n=126) or medical charts (n=77). For logistical reasons, this interim analysis includes updated data (as at April 2019) from patients with available EHRs (all USA; n=94). After a median follow-up of 30.3 months, median OS was 41.3 months (90% CI: 36.8–46.3) in the overall dataset (n=203) and 45.7 months (90% CI: 45.3–51.5) in Del19-positive patients (n=149). At 2 years, OS was 80%; OS in Asian patients was immature. Updated median TTF was 28.1 months (90% CI: 26.8–30.3) in the overall dataset, and 30.6 months (90% CI: 27.6–32.0) in Del19-positive patients. Outcomes were not affected by afatinib starting dose. Median TTF with osimertinib was 15.6 months (90% CI: 13.8–17.1) in the overall dataset, and 16.4 months (90% CI: 14.9–17.9) in Del19-positive patients. Encouraging OS and TTF were seen with sequential afatinib and osimertinib in patients with EGFR T790M-positive NSCLC, especially in Del19-positive patients, supporting the use of this regimen. Prior treatment with afatinib did not preclude prolonged TTF with second-line osimertinib (15.6 months overall; 16.4 months in Del19-positive patients). The final analysis, incorporating updated data from manual chart reviews and anticipated in early 2020, will provide further insights into the long-term OS of patients treated with sequential afatinib–osimertinib. 1. Hochmair MJ, et al. Future Oncol. 2018;14:2861–74.