Effectiveness and safety of osimertinib in patients with metastatic EGFR T790M-positive NSCLC: An observational real-world study

Abstract

Background: Osimertinib is an irreversible EGFR tyrosine kinase inhibitor (TKI) selective for both EGFR activating and T790M resistance mutations. In randomized controlled trials (RCTs), osimertinib showed encouraging efficacy in patients with advanced EGFR T790M mutation‐positive NSCLC; however, further investigation is needed in the real‐world where the patient population is more diverse. This study aimed to assess the effectiveness and safety of osimertinib in a real‐world setting. Methods: This observational study enrolled 47 patients with metastatic EGFR T790M‐positive NSCLC who progressed on prior EGFR TKI therapy and commenced osimertinib treatment between May and Oct 2016 in Macau. All patients received osimertinib 80 mg once daily until physician‐assessed disease progression. Primary endpoint was response rate (RR). Secondary endpoints included progression free survival (PFS), adverse events (AEs), T790M testing characteristics, and treatment patterns. Results: All patients had stage IV adenocarcinoma and 23.4% had brain metastases; median age was 59.0 years (range 37‐83 years) and 68.1% were female. Prior treatments included EGFR TKI targeted therapy (100%), chemotherapy (46.8%), radiation (19.1%), and immunotherapy (2.1%). 57.5% of patients received osimertinib as a second line therapy. T790M mutation was detected in either plasma (46.8%) or tissue/cytology (42.6%) samples; sample type was unknown in 5 (10.6%) patients. At data cut‐off (15 Jun 2017), 22 patients were still on osimertinib therapy. Physician‐assessed RR was 53.2% (95% CI 38.1‐67.9%; 6.4% complete response; 46.8% partial response) and 38.3% had stable disease. Median PFS was 9.6 months (95% CI 5.6‐10.9 months). Frequency of all AEs and AEs grade 3 were 38.3% and 4.3%, respectively. Most common AEs were rash (14.9%), fatigue (12.8%), and nausea (10.6%). Pneumonitis was reported in 1 patient (2.1%). Conclusions: Real‐world physician‐assessed RR and PFS with osimertinib appear comparable to that reported in RCTs; no new safety signals were observed. Our data corroborate the findings of RCTs and suggest that osimertinib provides encouraging effectiveness and similar safety when used in real‐world clinical practice.