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Published on: November 22, 2021
First-Line Osimertinib for Previously Untreated Patients With NSCLC and Uncommon EGFR Mutations: The UNICORN Phase 2
Yusuke Okuma1, Kaoru Kubota2, Mototsugu Shimokawa3
1Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
Importance:
Non-small cell lung cancer (NSCLC) with uncommon EGFR mutations is a rare subgroup, composing 14% of all EGFR mutations.
Objective:
To determine the usefulness of osimertinib in previously untreated patients with metastatic NSCLC harboring uncommon EGFR mutations, excluding exon 20 insertion mutations.
Design, Setting, And Participants:
This multicenter, open-label, single-group, phase 2 nonrandomized clinical trial enrolled patients from April 10, 2020, to May 31, 2022, with a follow-up of 6 months from the date the last patient was enrolled. The study enrolled 42 patients with uncommon EGFR mutations, of whom 40 were eligible.
Intervention:
Osimertinib, 80 mg once daily, was administered orally to patients.
Main Outcomes And Measures:
The primary end point was the overall response rate (ORR). The secondary end points were disease control rate (DCR), progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), duration of response (DoR), and safety of osimertinib. Patients were included in the study on an intention-to-treat basis.
Results:
Of the 40 eligible patients, 22 were men (55.0%) and the median age was 72 years (range, 39.0-88.0 years). The most common mutations were G719X (20 [50.0%]), S768I (10 [25.0%]), and L861Q (8 [20.0%]). The ORR was 55.0% (90% CI, 40.9%-68.5%) and the DCR was 90.0% (95% CI, 76.3%-97.2%). The median PFS was 9.4 months (95% CI, 3.7-15.2 months) after a median follow-up of 12.7 months (range, 2.7-30.7 months). The median TTF was 9.5 months (95% CI, 5.6-30.3 months), median OS was not reached (NR; 95% CI, 19.3 months to NR), and median DoR was 22.7 months (95% CI, 9.5 months to NR). The ORR for patients with solitary or compound uncommon EGFR mutations was 45.5% (90% CI, 26.9%-65.3%) and 66.7% (90% CI, 43.7%-83.7%), respectively. Median PFS for patients with solitary or compound uncommon EGFR mutations was 5.4 months (95% CI, 3.6-22.7 months) and 9.8 months (95% CI, 5.1 months to NR), respectively. Median OS for patients with solitary or compound uncommon EGFR mutations was 23.0 months (95% CI, 12.3 months to NR) and NR, respectively. Median DoR for patients with solitary or compound uncommon EGFR mutations was 22.7 months (95% CI, 3.6-22.7 months) or NR (95% CI, 5.7 months to NR), respectively. Grade 3 or 4 adverse events were reported by 11 patients (27.5%), and 5 patients (12.5%) developed interstitial lung disease. All adverse events were manageable, and there were no treatment-related deaths.
Conclusions And Relevance:
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. The results support the use of osimertinib as a treatment option for this patient population.
Trial Registration:
Japan Registry of Clinical Trials Identifier: jRCTs071200002.
Insights
Osimertinib demonstrated significant clinical activity in previously untreated patients with metastatic non-small cell lung cancer (NSCLC) harboring uncommon EGFR mutations. This targeted therapy offers a manageable safety profile, supporting its use in this rare patient subgroup.
Area of Science:
- Oncology
- Medical Research
- Clinical Trials
Background:
- Non-small cell lung cancer (NSCLC) with uncommon EGFR mutations represents a rare but distinct patient subgroup.
- Identifying effective treatments for these patients is crucial due to limited therapeutic options.
Purpose of the Study:
- To evaluate the efficacy and safety of osimertinib in treatment-naïve patients with metastatic NSCLC and uncommon EGFR mutations (excluding exon 20 insertions).
Main Methods:
- A multicenter, open-label, single-group, phase 2 nonrandomized clinical trial.
- 40 eligible patients received osimertinib 80 mg once daily.
- Primary endpoint: overall response rate (ORR); Secondary endpoints: disease control rate (DCR), progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), duration of response (DoR), and safety.
Main Results:
- The overall response rate (ORR) was 55.0% (90% CI, 40.9%-68.5%) and the disease control rate (DCR) was 90.0% (95% CI, 76.3%-97.2%).
- Median progression-free survival (PFS) was 9.4 months (95% CI, 3.7-15.2 months).
- Grade 3 or 4 adverse events occurred in 27.5% of patients, with manageable toxicity and no treatment-related deaths.
Conclusions:
- Osimertinib exhibits significant clinical activity and a manageable safety profile in previously untreated patients with metastatic NSCLC harboring uncommon EGFR mutations.
- These findings support osimertinib as a valuable treatment option for this specific patient population.
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