The exon 20 (ex20ins) insertion mutation is responsible for about 4 to 12% of the total EGFR gene mutations in patients with non-small cell lung cancer (NSCLC). These tumors are known to be less sensitive to tyrosine kinase inhibitors (TKI) targeting first or second-generation EGFR
AEX20 (UMIN000031929), a phase I/II, single-arm, multicenter, open-label, non-randomized trial that assessed the clinical efficacy of osimertinib in patients with advanced non-small–cell lung cancer (NSCLC) with ERexGF20ins, was presented during the American Association for Cancer Research (AACR) Annual Meeting 2021.
The study consists of two phases (Simon’s two-stage design). In phase I, 12 patients receive osimertinib 80mg/day until disease progression or severe toxicities. In phase II, nine patients receive the same dose of osimertinib if more than one patient achieves partial response or complete response in phase I.
The inclusion criteria of patients with advanced or metastatic NSCLC EGFRex20ins were:
Patients with other EGFR gene mutations, such as deletion of éxon 19, L858R, T790M, G719X, and L861Q, were excluded.
The primary endpoint was the objective response rate (ORR) evaluated by RECISTv1.1. Secondary outcomes included progression-free survival (PFS), overall survival (OS) and, safety profiles.
Blood sampling was obtained 4 weeks after the starting osimertinib to analyze pharmacokinetic parameters. Liquid biopsies were also performed for NGS (next–generation sequencing) before and after acquiring osimertinib tolerance in order to clarify the resistance mechanisms of 3rd generation TKI in EGFRex20ins.
A total of 12 patients were enrolled in phase I in six institutions. The average age was 63 years, six participants were female, eight patients had ECOG 0 and four had ECOG 1. The number of patients with phase IIIA, IIIb, IVA, and IVB NSCLC was 1, 1, 2, and 8, respectively.
The ORR was 0% and the disease control rate was 66.7%, being:
Therefore, the authors conclude that a regular dose of osimertinib has limited clinical activity in patients with NSCLC who have insertion mutation in exon 20.
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