Abstract 5733
Background
Osimertinib is an oral, potent, irreversible EGFR tyrosine kinase inhibitor (TKI) selective for sensitizing EGFR and EGFRT790M mutations and approved for the first-line treatment of patients with sensitizing EGFR-mutant NSCLC. EGFR exon 20 insertion mutations account for up to 4% of all EGFR mutations and are generally resistant to EGFR TKIs. Although osimertinib is active against in vitro models of EGFR exon 20 insertion mutation, its efficacy has not been prospectively studied. This phase II study has been performed to evaluate the efficacy of osimertinib in NSCLC patients with EGFR exon 20 insertion mutation who failed to standard chemotherapy (ClinicalTrials.gov, NCT03414814).
Methods
Patients received osimertinib 80mg orally once daily until disease progression, unacceptable toxicities, withdrawal, or no clinical benefits. Primary end point was investigator-assessed, confirmed objective response rate (ORR) as defined by RECIST version 1.1. Secondary end points were safety profiles, progression-free survival (PFS), overall survival (OS), and duration of response.
Results
Between Jan 2018 and Feb 2019, 15 patients received osimertinib as second-line (20%, n = 3) and ≥ third-line (n = 12) at stage 1 according to Simon’s minimax two-stage design (P0=0.10, P1=0.30; α = 0.05, β = 0.20). Median age was 61 years and female were 66.7%. ORR was 0% with mostly disease stabilization (stable disease, 46.7%, n = 7). Three patients who had EGFR exon 20 insertions at M766, A767, and unknown sites were still receiving osimertinib at the cut-off date (disease stabilization, 12, 7, and 7 months, respectively). Median PFS and OS were 3.5 months (95% CI 1.6-not reached) and not reached (1-year OS rate, 56.3%), respectively. Disease control rate at 6 months was 31.1%. The most frequently observed adverse events (AEs, all grades, %) were nausea (20%, n = 3), vomiting (20%, n = 3), anemia (13.3%, n = 2), and fever (13.3%, n = 2).
Conclusions
Osimertinib is well tolerated, but has limited clinical activity in NSCLC patients with EGFR exon 20 insertion mutation who failed to standard chemotherapy.
Clinical trial identification
NCT03414814.
Editorial acknowledgement
Legal entity responsible for the study
Tae Min Kim.
Funding
AstraZeneca.
Disclosure
T.M. Kim: Advisory / Consultancy, without any compensation: AstraZeneca; Advisory / Consultancy, without any compensation: Novartis; Advisory / Consultancy, without any compensation: Sanofi; Advisory / Consultancy, without any compensation: Bayer; Research grant / Funding (self), outside this work: AstraZeneca; Advisory / Consultancy, without any compensation: Takeda. B. Keam: Research grant / Funding (self), outside this work: AstraZeneca; Research grant / Funding (self), outside this work: MSD; Research grant / Funding (self), outside this work: ONO; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: MSD; Advisory / Consultancy: Genexine. D. Kim: Advisory / Consultancy, without any compensation: AstraZeneca; Advisory / Consultancy, without any compensation: Novartis; Advisory / Consultancy, without any compensation: Takeda. All other authors have declared no conflicts of interest. Linguistic correction
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