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
5344 - Global trends in population-based survival for 303,169 adults diagnosed with glioblastoma in 44 countries during 2000-2014 (CONCORD-3)
Presenter: Fabio Girardi
Session: Poster Display session 1
Resources:
Abstract
3088 - Spanish Survey of treatment recommendations for elderley patients with glioblastoma
Presenter: María Ángeles Vaz Salgado
Session: Poster Display session 1
Resources:
Abstract
3484 - Updated analysis of the National Registry of Nervous System Tumors in Spain (RETSINE). RETSINE: National Registry of Nervous System Tumors of the Spanish Research Group in Neuro-oncology (GEINO) and Spanish Infrequent and Orphan Tumors Group (GETHI)
Presenter: Isaac Ceballos Lenza
Session: Poster Display session 1
Resources:
Abstract
4737 - Development and validation of novel nomograms predicting survival of malignant ependymoma patients: A population-based study
Presenter: Alzhraa Abbas
Session: Poster Display session 1
Resources:
Abstract
4740 - Characteristics, incidence, and survival of primary cerebral lymphoma: A population based study
Presenter: Sherief Ghozy
Session: Poster Display session 1
Resources:
Abstract
5362 - Trends in Incidence and Survival Analyses of Adult-onset Medulloblastoma
Presenter: Feifei Lin
Session: Poster Display session 1
Resources:
Abstract
3868 - Meta of classical chemotherapy compared with high-dose chemotherapy combined with autologous stem cell transplantation in newly diagnosed medulloblastoma patients after radiotherapy
Presenter: Mengting Zhang
Session: Poster Display session 1
Resources:
Abstract
4446 - Effect of cumulative dose of maintenance temozolomide on overall survival in patients with high grade glia tumors: a single institution analysis
Presenter: Marta Nerone
Session: Poster Display session 1
Resources:
Abstract
5119 - Markers of systemic inflammation correlate with survival prognosis in patients with newly diagnosed brain metastases
Presenter: Angelika Starzer
Session: Poster Display session 1
Resources:
Abstract
3882 - Venous Thromboembolism and Intracranial Hemorrhage in Patients with High-grade Glioma
Presenter: Clara Borges
Session: Poster Display session 1
Resources:
Abstract