A single-arm, multicenter, phase II trial of osimertinib in patients with epidermal growth factor receptor exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations

Background: For patients with stage IV non-small-cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletions and exon 21 L858R mutations, osimertinib is the standard of care. Investigating the activity and safety of osimertinib in patients with EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations is of clinical interest. Patients and methods: Patients with stage IV non-small-cell lung cancer with confirmed EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations were eligible. Patients were required to have measurable disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate organ function. Patients were required to be EGFR tyrosine kinase inhibitor-naive. The primary objective was objective response rate, and secondary objectives were progression-free survival, safety, and overall survival. The study used a two-stage design with a plan to enroll 17 patients in the first stage, and the study was terminated after the first stage due to slow accrual. Results: Between May 2018 and March 2020, 17 patients were enrolled and received study therapy. The median age of patients was 70 years (interquartile range 62-76), the majority were female (n = 11), had a performance status of 1 (n = 10), and five patients had brain metastases at baseline. The objective response rate was 47% [95% confidence interval (CI) 23% to 72%], and the radiographic responses observed were partial response (n = 8), stable disease (n = 8), and progressive disease (n = 1). The median progression-free survival was 10.5 months (95% CI 5.0-15.2 months), and the median OS was 13.8 months (95% CI 7.3-29.2 months). The median duration on treatment was 6.1 months (range 3.6-11.9 months), and the most common adverse events (regardless of attribution) were diarrhea, fatigue, anorexia, weight loss, and dyspnea. Conclusions: This trial suggests osimertinib has activity in patients with these uncommon EGFR mutations.