- Osimertinib is effective and safe in patients with NSCLC and uncommon epidermal growth factor receptor (EGFR) mutations, with the best objective response rate (ORR) and PFS in patients with the L861Q mutation.
Why this matters
- About 10% of patients with EGFR-mutated NSCLC have uncommon mutations.
- Multicenter, open-label, single-arm, phase 2 study.
- 36 patients with NSCLC and uncommon EGFR mutations received osimertinib.
- Median follow-up, 20.6 months.
- Funding: AstraZeneca, others.
- ORR was 50%, median duration of response was 11.2 months, and disease control rate was 89%.
- Median PFS was 8.2 months; OS was 86% at 12 months and 56% at 18 months.
- 81% of patients died or had disease progression.
- The most frequently occurring uncommon EGFR mutations were G719X (53%), L861Q (25%), and S768I (22%).
- Among these, osimertinib had the greatest efficacy and PFS in the L861Q mutation.
- L861Q: ORR, 78%; PFS, 15.2 months;
- G719X: ORR, 53%; PFS, 8.2 months; and
- S768I: ORR, 38%; PFS, 12.3 months.
- Median PFS was shorter in those with central nervous system metastases at baseline (5.4 vs 9.8 months).
- 94% experienced ≥1 adverse event (AE), but only 6% reported grade ≥3 AEs.
- Small sample size.