Abstract 1299P
Background
Epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) have shown efficacy for the treatment of EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC). However, patients (pts) progress despite initial response to 1st/2nd generation (1G/2G) TKIs.
Methods
Clinical characteristics, treatment patterns, attrition rate and survival outcomes were assessed in a retrospective study of 896 pts initiating first line (1L) TKI between Jan 2015 - Jun 2018 in 49 sites in 7 European countries and Israel (data collection: May to Dec 2019). Kaplan-Meier methods were used to estimate median progression free survival (mPFS), overall survival (mOS) and time to treatment discontinuation (mTTD) [months (m) and (95% CI)] from 1L start.
Results
Baseline characteristics: median age 68 y; 64.1% female; 51.3% never smokers; 53.9% exon 19 deletion, 31.4% L858R, 14.7% uncommon EGFR mutations; 22.1% brain metastases; 69.6% ECOG 0-1. 1L TKI: 45.4% afatinib, 27.3% erlotinib, 27.2% gefitinib. Median follow-up from 1L start: 21.5 m. 14.6% pts continued 1L therapy at data collection. Of 765 pts stopping 1L, reasons were 75.0% progression, 11.2% death and 13.7% other. 1L mPFS was 13.0 (12.3,14.1) m and mTTD 12.6 (11.8,13.3) m. 32.7% (250/765) did not receive any 2L therapy. 515 pts started 2L therapy [chemotherapy 31.7% (163/515); osimertinib 59.8% (308/515)]. Of 395 pts discontinuing 2L, reasons were 59.7% progression, 22.0% death and 18.2% other. 2L median duration was 2.3 (2.0,2.8) m for chemotherapy and 10.9 (9.4,12.4) m for osimertinib. 20.4% (183/896) pts received 3L, of which 16.4% received osimertinib, and 6.1% (55/896) pts started 4L. Of 765 pts stopping 1L, 76.1% were tested for T790M at any time with 40.0% positive. 262/306 positive, 34/275 negative and 12/314 untested pts received osimertinib in 2L. In total 44.3% (339/765) started osimertinib post-1L. Overall mOS was 26.2 (23.6,28.4) m.
Conclusions
This is one of the largest studies with European pts treated with 1L 1G/2G TKIs. In real-world setting, 1/3 of pts never received 2L therapy, 3/4 were tested for T790M and <1/2 received osimertinib after 1L. More efficient use of EGFR TKIs is needed for better outcomes.
Clinical trial identification
NCT04031898.
Editorial acknowledgement
Editorial assistance to authors was provided by Ana Maria Iordan, MD (MedInteractiv, Bucharest, Romania).
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
A. Addeo: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Travel/Accommodation/Expenses: Merck; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Takeda; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Merck Sharpe & Dohme; Advisory/Consultancy: Boehringer Ingelheim . M.J. Hochmair: Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda. U. Janzic: Honoraria (self), Honoraria (institution): AstraZeneca; Honoraria (self), Honoraria (institution): Boehringer Ingelheim; Honoraria (self), Honoraria (institution): Roche; Honoraria (self), Honoraria (institution): Merck Sharp & Dohme; Honoraria (self), Honoraria (institution): Pfizer; Honoraria (institution): Novartis ; Honoraria (institution): Bristol-Myers Squibb. E. Dudnik: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis ; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Sharp & Dohme. A. Charpidou: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self): Merck Sharp & Dohme; Honoraria (self): Merck . A. Pluzanski: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche. T-E. Ciuleanu: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Astellas; Advisory/Consultancy: Janssen; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Amgen; Advisory/Consultancy: Roche; Advisory/Consultancy: Novartis ; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Lilly; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Servier; Advisory/Consultancy: AD Pharma. J. Elbaz R. Lupu: Full/Part-time employment: AstraZeneca. R.G. Ott: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. N. Peled: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Eli Lilly ; Honoraria (self), Advisory/Consultancy: Foundation Medicine; Honoraria (self), Advisory/Consultancy: Gaurdant360; Honoraria (self), Advisory/Consultancy: Genesort; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy: NovellusDx; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Takeda. All other authors have declared no conflicts of interest.