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
2185 - Sequential treatment with afatinib followed by 3rd generation EGFR-TKI – subgroup analysis of the GIDEON trial: a prospective non-interventional study (NIS) in EGFR mutated NSCLC patients in Germany
Presenter: Wolfgang Brückl
Session: Poster Display session 1
Resources:
Abstract
1524 - Effectiveness of sequencing TKIs in patients with EGFR mutation-positive Non-small-Cell Lung Cancer (NSCLC): A French National medico administrative claim database analysis
Presenter: Nicolas Girard
Session: Poster Display session 1
Resources:
Abstract
5733 - Phase II study of osimertinib in NSCLC patients with EGFR exon 20 insertion mutation: A multicenter trial of the Korean Cancer Study Group (LU17-19)
Presenter: Tae Min Kim
Session: Poster Display session 1
Resources:
Abstract
5440 - Different stories for different EGFR exon 19 deletion variants
Presenter: Chao Zhao
Session: Poster Display session 1
Resources:
Abstract
2982 - Safety and activity of alflutinib in patients with advanced EGFR T790M mutation non-small cell lung cancer who progressed after EGFR-TKI therapy
Presenter: Yuan-Kai Shi
Session: Poster Display session 1
Resources:
Abstract
4002 - Afatinib followed by osimertinib in patients with EGFR mutation-positive (EGFRm+) advanced NSCLC: updated data from the GioTag real-world study
Presenter: Maximilian Hochmair
Session: Poster Display session 1
Resources:
Abstract
2941 - Treatment patterns of EGFR mt+ NSCLC IV pts: Real world data of the NOWEL network
Presenter: Julia Roeper
Session: Poster Display session 1
Resources:
Abstract
4154 - TP53 mutations predicts worse prognosis in EGFR-mutated NSCLC patients receiving TKIs in first- or further line of treatment
Presenter: Matteo Canale
Session: Poster Display session 1
Resources:
Abstract
1175 - HER3 ligand heregulin expression and clinical implication in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer treated with EGFR-tyrosine kinase inhibitors
Presenter: Kimio Yonesaka
Session: Poster Display session 1
Resources:
Abstract
2023 - Patients with brain metastases treated with afatinib in clinical practice – results from the prospective non-interventional study GIDEON
Presenter: Eckart Laack
Session: Poster Display session 1
Resources:
Abstract