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
4883 - A New Population Model Validated Pharmacokinetic Similarity of HLX01 and Rituximab in B-Cell Lymphoma
Presenter: Yuankai Shi
Session: Poster Display session 1
Resources:
Abstract
4908 - Efficacy of salvage therapy in the treatment of Helicobacter pylori-positive gastric low-grade mucosa-associated lymphoid tissue lymphoma
Presenter: Sung-Nam Lim
Session: Poster Display session 1
Resources:
Abstract
2360 - Mutational analysis of extranodal marginal zone lymphoma using next generation sequencing
Presenter: Seok Jae Huh
Session: Poster Display session 1
Resources:
Abstract
2430 - Clinical features, treatment and outcomes of colon and rectum mucosa-associated lymphoid tissue (MALT) lymphoma: Literature reviews published in English between 1993 and 2017
Presenter: Jeong Yeon Kim
Session: Poster Display session 1
Resources:
Abstract
4654 - Splenic marginal zone lymphoma: clinical characteristics and prognostic factors in a series of 52 patients
Presenter: Guldane Cengiz Seval
Session: Poster Display session 1
Resources:
Abstract
1732 - Safety and efficacy of Bendamustine and Rituximab (BR) regimen in Indian Chronic Lymphocytic Leukemia patients
Presenter: Ajay Gogia
Session: Poster Display session 1
Resources:
Abstract
5784 - N-terminal B-type natriuretic peptide (NT-proBNP) as an independed prognostic marker for patients with newly diagnosed multiple myeloma complicated by dialysis-dependent renal failure
Presenter: Sergey Semochkin
Session: Poster Display session 1
Resources:
Abstract
836 - The first-line effect of Bortezomib-based Therapy on Clinical Outcomes for Taiwanese Patients with multiple myeloma
Presenter: Ching-Liang Ho
Session: Poster Display session 1
Resources:
Abstract
2085 - Impact of Donor Lymphocyte Infusion in Relapsing Myeloid Neoplasms Post Allogeneic Hematopoietic Stem Cell Transplantation
Presenter: Hanafy Hafez
Session: Poster Display session 1
Resources:
Abstract
6079 - Invasive fungal diseases in patients with Hodgkin’s lymphoma before and after allogeneic hematopoietic stem cell transplantation
Presenter: Marina Popova
Session: Poster Display session 1
Resources:
Abstract