Abstract 3832
Background
Approximately 20%–30% of patients (pts) with EGFR mutation-positive NSCLC present with CNS metastases at the time of diagnosis of advanced disease. CNS metastases are associated with a poor prognosis. Osimertinib is a third-generation, irreversible, oral EGFR-tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR-TKI sensitising (EGFRm) and EGFR T790M mutations and in clinical trials has demonstrated efficacy in NSCLC CNS metastases. ASTRIS is the largest ongoing, international, real-world study of osimertinib in EGFR T790M positive advanced NSCLC (NCT02474355). We report a subset analysis of pts with CNS metastases.
Methods
Eligible pts with stage IIIB/IV EGFR T790M positive NSCLC previously treated with an EGFR-TKI received osimertinib 80 mg once-daily. Investigator-assessed (IA) progression-free survival (PFS), clinical response and time to treatment discontinuation (TTD) were analysed in a subset of pts with CNS (leptomeningeal and/or brain) metastases at baseline (BL). Follow-up brain imaging was not mandatory.
Results
From 18 September 2015 to 15 October 2018, 3015 pts across 16 countries had received ≥1 dose of osimertinib (full analysis set [FAS]); 882 (29%) pts presented with CNS metastases at BL. BL demographics were similar between this subset and the FAS (female: 63%/64%; Asian: 69%/69%; median age (range): 61 (27–88) years/62 (27–92); WHO performance status 2: 15%/11%). IA response rates were consistent across the two groups, while median PFS and TTD appeared to be slightly lower in the CNS subset (Table). Overall survival data are immature.Table:
1521P Clinical outcomes for pts with EGFR T790M advanced NSCLC and CNS metastases at BL
Clinical outcomes | FAS Osimertinib 80 mg (N = 3015) | CNS subset Osimertinib 80 mg (N = 882) |
---|---|---|
Response rate*, % (95% CI) | 57 (55, 59) | 59 (55, 62) |
Best overall response†, n (%) Responding Stable disease Progressive disease Unknown | 1655 (55) 1043 (35) 202 (7) 115 (4) | 485 (55) 274 (31) 66 (7) 57 (6) |
Median PFS, months (95% CI) | 11.1 (11.0, 12.0) | 9.7 (9.2, 10.5) |
Median TTD, months (95% CI) | 13.5 (12.6, 13.9) | 11.1 (10.1, 12.1) |
CI, confidence interval
*Response rate is defined as the percentage of pts with a best response of ’Responding’ by investigator assessment, based on pts with ≥1 documented response assessment. 95% CI is defined by Clopper-Pearson method †Best overall response is defined as the best response by investigator assessment. Pts with no assessments were considered as ’Unknown’
Conclusions
In a real-world setting, over half of pts with EGFR T790M positive advanced NSCLC and CNS metastases responded to treatment with osimertinib 80 mg. These findings support previous clinical research showing clinically meaningful CNS efficacy with osimertinib in advanced NSCLC.
Clinical trial identification
NCT02474355.
Editorial acknowledgement
Bernadette Tynan, MSc, of iMed Comms, Macclesfield, UK, an Ashfield Company, part of UDG Healthcare plc, funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
M. Provencio: Advisory / Consultancy: BMS, MSD, AstraZeneca, BI; Travel / Accommodation / Expenses: MSD, AstraZeneca. D. Kim: Research grant / Funding (institution): Alpha Biopharma, AstraZeneca/MedImmune, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan. B.C. Cho: Honoraria (institution): Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, Boehringer Ingelheim, Roche, BMS, Pfizer, Eli Lilly, Takeda, TheraCanVac Inc.; Advisory / Consultancy: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, Boehringer Ingelheim, Roche, BMS, Pfizer, Eli Lilly, Takeda, TheraCanVac Inc.; Speaker Bureau / Expert testimony: Novartis; Research grant / Funding (institution): Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD; Shareholder / Stockholder / Stock options: TheraCanVac Inc.; Licensing / Royalties: Champions Oncology. K. Park: Advisory / Consultancy: AMGEN, AstraZeneca, Astellas, BluePrint, Eli Lilly, Hanmi, KHK, MSD, Boehringer Ingelheim, Roche, Merck KGaA, Ono; Speaker Bureau / Expert testimony: Boehringer Ingelheim; Research grant / Funding (self): AstraZeneca. R. Migliorino: Advisory / Consultancy: AstraZeneca, MSD, BI, Pfizer, Roche, BMS; Speaker Bureau / Expert testimony: AstraZeneca, MSD, BI, Pfizer, Roche, BMS; Travel / Accommodation / Expenses: AstraZeneca, MSD, BI, Pfizer, Roche, BMS. M. Tiseo: Advisory / Consultancy: AstraZeneca, BMS, MSD, Boehringer Ingelheim, Takeda; Research grant / Funding (institution): AstraZeneca. Q. Zhou: Honoraria (self): AstraZeneca, Roche. A. Santo: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca, Roche. A. Ardizzoni: Honoraria (self): MSD, BMS, Pfizer, Eli Lilly; Advisory / Consultancy: MSD, Roche; Research grant / Funding (institution): BMS, Celgene, Roche. Y. Wu: Honoraria (self): AstraZeneca, Roche, Eli Lilly, Pfizer, MSD, BMS, Boehringer Ingelheim; Advisory / Consultancy: AstraZeneca, Roche, Boehringer Ingelheim; Research grant / Funding (institution): AstraZeneca, Roche. S. Kim: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca. M. Miranda: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca PLC. A. Fernandes: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. F. de Marinis: Honoraria (self), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Roche, Celgene, MSD, BMS, AstraZeneca, Takeda, Pfizer; Research grant / Funding (self): Boehringer Ingelheim, MSD. All other authors have declared no conflicts of interest.
Resources from the same session
4811 - Comprehensive genomic profiling of thymic carcinoma in a sample Chinese population
Presenter: Baohui Han
Session: Poster Display session 1
Resources:
Abstract
2045 - The analysis of treatment sequences and clinical outcomes of thymic carcinoma
Presenter: Arakaki Motoko
Session: Poster Display session 1
Resources:
Abstract
4785 - Transcriptomic Difference of Thymoma and Thymic Carcinoma
Presenter: Naixin Liang
Session: Poster Display session 1
Resources:
Abstract
2864 - A Phase II Trial of Preoperative Chemoradiotherapy and Pembrolizumab for Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC)
Presenter: Seoyoung Lee
Session: Poster Display session 1
Resources:
Abstract
5015 - The study of tumor associated exosomes in crosstalk between esophageal carcinoma and lymphatic endothelial cells
Presenter: Weimin Mao
Session: Poster Display session 1
Resources:
Abstract
1339 - Up-regulation of IBSP expression predicts poor prognosis of Esophageal Squamous Cell Carcinoma patients
Presenter: Mingyue Wang
Session: Poster Display session 1
Resources:
Abstract
4083 - PD-L1 expression in primary tumour vs metastatic samples in the Phase 3 MYSTIC study in first-line metastatic (m) NSCLC
Presenter: Niels Reinmuth
Session: Poster Display session 1
Resources:
Abstract
5113 - Assessing the impact of subsequent checkpoint inhibitor (CPI) treatment on overall survival: post hoc analyses from the phase 3 JAVELIN Lung 200 study of avelumab vs docetaxel in platinum-treated locally advanced/metastatic non-small cell lung cancer (NSCLC)
Presenter: Fabrice Barlesi
Session: Poster Display session 1
Resources:
Abstract
4256 - Long-term avelumab treatment in patients with advanced non-small cell lung cancer (NSCLC): post hoc analyses from JAVELIN Solid Tumor
Presenter: Borys Hrinczenko
Session: Poster Display session 1
Resources:
Abstract
4305 - Effectiveness and safety of nivolumab in the treatment of lung cancer patients in France: Updated survival and subgroup analysis from the real-world EVIDENS study
Presenter: Fabrice Barlesi
Session: Poster Display session 1
Resources:
Abstract