Efficacy of osimertinib in advanced T790M-positive NSCLC after progression to prior EGFR-TKI: real world data from a Brazilian cohort.

Abstract

OBJECTIVES: Osimertinib is a third-generation EGFR inhibitor with activity against both sensitizing and resistance mutations. Following results of the phase III study, AURA3, which led to the approval of osimertinib worldwide, we have conducted ASTRIS with the aim of confirming the efficacy and safety of osimertinib. METHODS: This is a phase IV, international, multicentric, open trial assessing the efficacy and safety of osimertinib at a dose of 80mg daily, orally. Eligible patients were those with diagnosis of T790M-positive NSCLC on progression after prior EGFR-TKI. Herein, we present the Brazilian experience at ASTRIS. RESULTS: Eighty-eight patients were enrolled in Brazil between August, 2015 and March, 2017. The median age was 34-89 (years), and most were females (66%). Fifty-four patients (61%) had received prior therapy with erlotinib, forty-two (48%) with gefitinib, and 3 (3%) with afatinib. Exon 19 deletions were the most common primary mutation in EGFR, present in 55 cases (62.5%), followed by L858R in 24 cases (27%). The response rate was 58.2% (95%CI = 46.6-69.2), and median progression-free survival was 9.4 months (95%CI = 8.2-not reached). The most common AE was pneumonia (5 cases). Only 1 patient (1.1%) had a pneumonitis-like event and 2 patients (2.3%) had a prolongation of the QTc interval. CONCLUSION: In a real-world setting, osimertinib constitutes a safe and effective therapeutic option for Brazilian patients with advanced T790M-positive NSCLC after progression on a prior EGFR-TKI, including those patients with central nervous system metastasis. Our findings support previous observations and add valuable information regarding osimertinib effectiveness in Brazilian patients.