Abstract 529P
Background
Osimertinib is an EGFR TKI selective for both EGFR TKI sensitizing and Thr790Met resistance mutations. While intracranial activity of osimertinib has been observed in patient subgroups within larger trials, a study focusing exclusively on patients with brain metastases has not yet been reported. We assessed the intracranial activity of osimertinib in EGFR-mutant, NSCLC patients with asymptomatic brain metastases, either as first-line therapy or following progression in pre-treated Thr790Met-positive patients.
Methods
In this phase 2, open-label, two-arm study we enrolled patients with EGFR-mutant, metastatic NSCLC and at least one asymptomatic brain metastasis of 4 mm or larger in diameter. Treatment-naïve patients (arm A) and Thr790Met-positive patients who progressed on EGFR-TKI therapy (arm B) received osimertinib 80 mg once daily. Dose escalation to 160 mg once daily was performed in cases of intracranial progression without symptomatic systemic progression. The primary endpoint in both arms was intracranial metastasis response. Here we present a preliminary analysis upon the trial outstanding results.
Results
Between 31/05/16 - 30/08/18 (data cutoff) 21 patients with asymptomatic brain metastases started osimertinib treatment (arm A = 15, arm B = 5 arm C = 1). Median duration of follow-up was 43 weeks. Intracranial response was achieved in 11 (73%; 95% CI 45%-92%) of 15 treatment-naïve patients (arm A) and in four (80%; 95% CI 28%-99%) of five previously treated Thr790Met-positive patients (arm B). Dose escalation was performed in four patients (arm A = 2, Arm B = 2), with one continuous response. 10 of 15 patients (67%) in arm A and 1 of 5 patients (20%) in arm B continue responding to osimertinib 80 mg at data cutoff. Toxicity side effects were similar to previously reported studies.
Conclusions
Osimertinib shows equal intracranial and systemic activity with minor side effects in EGFR-mutant, treatment-naïve NSCLC and in previously treated Thr790Met-positive patients. Therefore, we suggest that osimertinib is a reasonable first treatment option for patients with EGFR-positive NSCLC and newly diagnosed asymptomatic brain metastases, and may postpone or even defer the need for brain irradiation.
Clinical trial identification
NCT02736513.
Editorial acknowledgement
Legal entity responsible for the study
Nir Peled.
Funding
AstraZeneca.
Disclosure
N. Peled: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BI, BMS, Lilly, MSD, Novartis, Pfizer, Roche, FMI, NovellusDx, Gaurdant360, Takeda. E. Dudnik: Advisory / Consultancy, Travel / Accommodation / Expenses: BI, Merck/MSD, Roche Pharmaceuticals, AstraZeneca. All other authors have declared no conflicts of interest.
Resources from the same session
184P - Expression pattern of CDK12 protein in gastric cancer and its positive correlation with CD8+ cell density and CCL12 expression
Presenter: Jun Ji
Session: Poster display session
Resources:
Abstract
185P - Evaluation of the effect of cholesorption on the concentration of TNF-α in the serum of the blood in tumours of the biliopancreatoduodenal zone
Presenter: Marufjon Salokhiddinov
Session: Poster display session
Resources:
Abstract
186P - Efficacy and safety of sorafenib following hepatic resection in patients with hepatocellular carcinoma: A meta-analysis
Presenter: Yang Yuan
Session: Poster display session
Resources:
Abstract
187P - Correlation between spleenic dose and grade of hematological toxicity in chemoradiation of stomach
Presenter: Umesh Velu
Session: Poster display session
Resources:
Abstract
188P - Survival and prognostic factors in cholangiocarcinoma: A single-center experience
Presenter: Sonngwit Payapwattanawong
Session: Poster display session
Resources:
Abstract
189P - Stereotactic body radiotherapy in primary hepatocellular carcinoma and oligometastatis to liver: A single Institution experience
Presenter: Sayan Paul
Session: Poster display session
Resources:
Abstract
190P - Details of response with first-line gemcitabine and nab-paclitaxel therapy in patients with advanced pancreatic cancer
Presenter: Yusuke Nagata
Session: Poster display session
Resources:
Abstract
191P - Assessment of efficacy and safety of sorafenib versus no treatment in Egyptian hepatocellular carcinoma patients
Presenter: Noha El Baghdady
Session: Poster display session
Resources:
Abstract
192P - Clinical importance of the determination of interleukin-6 in bile and blood in tumours of biliopancreatoduodenal zone
Presenter: Marufjon Salokhiddinov
Session: Poster display session
Resources:
Abstract
193P - Metastatic carcinoma gall bladder: A clinicoepidemiological profile of Indian patients
Presenter: Anvesh Rathore
Session: Poster display session
Resources:
Abstract