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
339TiP - PACIFIC-5: Phase III study of durvalumab after either concurrent or sequential chemoradiotherapy (CRT) in patients with stage III NSCLC
Presenter: Yi-Long Wu
Session: Poster display session
Resources:
Abstract
340TiP - A multicenter, randomized, controlled, phase II trial exploring adjuvant combined therapy of apatinib and SHR-1210 (anti-PD-1), in patients with hepatocellular carcinoma at high risk of recurrence after radical resection
Presenter: Shida Yan
Session: Poster display session
Resources:
Abstract
347P - Relationship between modified surgical margin and prognosis of cutaneous squamous cell carcinoma
Presenter: Yukiko Teramoto
Session: Poster display session
Resources:
Abstract
348P - Malignant melanoma: A study of clinical profiles and treatment outcomes in Indian patients
Presenter: Sorun Shishak
Session: Poster display session
Resources:
Abstract
349P - Flavonoids from ethanol extracts of euphorbia hirta inhibit melanoma growth and metastatic potential
Presenter: Shubhra Mishra
Session: Poster display session
Resources:
Abstract
350P - Low-dose cisplatin and 5-fluorouracil combined concurrent chemoradiotherapy for unresectable cutaneous squamous cell carcinoma: Analysis of 23 cases
Presenter: Azusa Hiura
Session: Poster display session
Resources:
Abstract
353P - A prediction model for the intents regarding life-sustaining treatment decisions in patients with terminal cancer
Presenter: Yoonsun Kim
Session: Poster display session
Resources:
Abstract
354P - Predictive factors and survival outcomes with stereotactic body radiation therapy in treatment of oligometastases in colorectal cancer
Presenter: Vibhay Pareek
Session: Poster display session
Resources:
Abstract
355P - Cost analysis and overview of single versus multiple fraction palliative radiotherapy for painful bone metastasis
Presenter: Vinodhkumar Selvaraj
Session: Poster display session
Resources:
Abstract
356P - Observational study on role of crude cannabis in pain control and quality of life in terminally ill cancer patients: An Indian perspective
Presenter: Vidyasagar Dusi
Session: Poster display session
Resources:
Abstract