First-Line Osimertinib for Patients With Metastatic NSCLC Harboring Uncommon EGFR Mutations

Results from the nonrandomized, phase 2 UNICORN trial demonstrated that osimertinib in the first-line setting is a clinically effective and safe treatment option for patients with metastatic non-small cell lung cancer (NSCLC) harboring an uncommon EGFR mutation. 

According to Yusuke Okuma, MD, PhD, National Cancer Center Hospital, Tokyo, Japan, and coauthors, “[NSCLC] with uncommon EGFR mutations is a rare subgroup, composing 14% of all EGFR mutations.”

In this multicenter, open-label, single group study, 40 patients with NSCLC and G719X, S768I, and L81Q mutations who had not previously been treated received 80 mg oral osimertinib once daily. The primary end point was overall response rate (ORR). Secondary end points included disease control rate (DCR), progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), duration of response (DOR), and safety. 

At a follow up of 6 months after the last patient was enrolled, ORR was 55% and DCR was 90%. Median PFS was 9.4 months, after a follow up of 12.7 months. Median TTF was 9.5 months, median DOR was 22.7 months. The median OS was not reached. For patients with solitary or compound uncommon EGFR mutations, ORR was 45.5% and 66.7% and median PFS was 5.4 months and 9.8 months. Among patients with solitary uncommon EGFR mutations, median OS was 23 months and median DOR was 22.7 months while patients with compound uncommon EGFR mutations did not respond. Grade 3/4 adverse events were reported by 11 patients, and 5 patients developed interstitial lung disease. All adverse events were manageable and there were no treatment-related deaths. 

“Osimertinib showed clinical activity with manageable toxic effects among previously untreated patients with metastatic NSCLC harboring uncommon EGFR mutations other than exon 20 insertion mutations,” concluded Dr Okuma and coauthors. “The results support the use of osimertinib as a treatment option for this patient population.”

Source: 

Okuma Y, Kubota K, Shimokawa M, et al. First-line osimertinib for previously untreated patients with NSCLC and uncommon EGFR mutations. JAMA Oncol. Published online: November 22, 2023. doi:10.1001/jamaoncol.2023.5013