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
Resources from the same session
3690 - PD-L1 expression in resected undifferentiated pleomorphic sarcoma and its clinical implications
Presenter: Kyoungmin Lee
Session: Poster Display session 1
Resources:
Abstract
2013 - PD-L1 expression as a potential therapeutic target and prognostic biomarker in well-differentiated and dedifferentiated liposarcoma.
Presenter: Heejung Chae
Session: Poster Display session 1
Resources:
Abstract
5021 - Soft tissue sarcomas express a distinct mRNA immune profile
Presenter: Viktor Grünwald
Session: Poster Display session 1
Resources:
Abstract
3029 - The molecular landscape of fusion genes in endometrial stromal sarcomas include three nosological entities with different natural history
Presenter: Mehdi Brahmi
Session: Poster Display session 1
Resources:
Abstract
3914 - Clinical validation of a novel assay for the detection of diagnostic alterations in sarcomas
Presenter: Lauren Mc Connell
Session: Poster Display session 1
Resources:
Abstract
1912 - A prospective correlative trial of personalized patient-derived xenograft (PDX) as avatars for drug therapy in patients with metastatic or recurrent soft tissue sarcomas (STS).
Presenter: Kanan Alshammari
Session: Poster Display session 1
Resources:
Abstract
5097 - Fusion of immortalized myoblasts induces genomic instability that drives tumor development and progression.
Presenter: Candice Merle
Session: Poster Display session 1
Resources:
Abstract
1383 - let-7a suppress Ewing sarcoma CSCs' malignant phenotype through forms a positive feedback regulation loop with lin28 via STAT3
Presenter: Xu Jiang
Session: Poster Display session 1
Resources:
Abstract
3386 - Myoepithelial Tumors of Soft Tissues and Extraskeletal Myxoid Chondrosarcomas feature a distinct transcriptional pattern
Presenter: Dominga Racanelli
Session: Poster Display session 1
Resources:
Abstract
1844 - In Vivo Efficacy and Enhanced Tumor Accumulation of Liposomal Vinorelbine (TLC178) in Human Sarcoma Xenograft Mice Model
Presenter: Wan-ni Yu
Session: Poster Display session 1
Resources:
Abstract