Abstract 482P
Background
First-line afatinib significantly improved median progression-free survival (PFS) in pts with EGFRm+ NSCLC vs chemotherapy (CT) in LUX-Lung (LL) 3/6 (HR [95% CI]: 0.58 [0.43, 0.78]/0.28 [0.20, 0.39]), and vs gefitinib in LL7 (0.73 [0.57, 0.95]). We conducted a phase IIIb study of afatinib in a broader patient population, similar to real-world practice, of treatment-naïve or CT pre-treated pts with EGFRm+ NSCLC. Here we present an interim analysis.
Methods
EGFR TKI-naïve pts with locally advanced/metastatic EGFRm+ NSCLC and ECOG PS 0–2 received afatinib 40 mg/day; dose reduction was permitted (min. 20 mg/day). Primary endpoint: adverse events (AEs; descriptive fashion). Efficacy was assessed and post-hoc subgroup analysis conducted.
Results
479 pts were included (data cut-off: 30/04/18): Caucasian/Asian: 97%/2%; female: 66%; 1st/2nd/≥3rd-line therapy: 78%/17%/5%; ECOG PS 0 or 1/2: 92%/8%; brain metastases: 17%; common/uncommon [C/U] mutations: 87%/13%. Median time on afatinib: 359 days. Objective response rate: 46%. Disease control rate: 86%. Median time to symptomatic progression (TTSP) and PFS were 14.9 (95% CI: 13.8, 17.6) and 13.4 (11.8, 14.5); subgroup analysis is in the table. Most common grade ≥3 afatinib-related AEs were diarrhea (16%) and rash (11%). AEs led to dose reduction in 258 (54%) pts (most frequently diarrhea 25%, rash 11%) and to afatinib discontinuation in 105 (22%) pts (malignant neoplasm progression 3%, diarrhea 3% [rash 0.8%]). Afatinib-related serious AEs occurred in 39 (8%) pts.
Conclusions
This analysis indicates a predictable and manageable safety profile for afatinib, consistent with the pivotal LL trials, and encouraging efficacy findings in this broad patient population. As expected, TTSP/PFS were longer for pts with ECOG PS 0/1 vs 2, and for pts with Del 19 or L858R mutations, vs those with uncommon mutations, which may be due to the high prevalence (44%) of pts with exon 20 insertions included in this study.
Table: 482P
TTSP, mos | PFS, mos | |||
---|---|---|---|---|
Baseline characteristic (n) | Median | 95% CI | Median | 95% CI |
Line of tx | ||||
1 (374) | 15.6 | 14.1, 18.5 | 13.8 | 12.6, 15.2 |
2 (81) | 14.7 | 11.3, 20.6 | 13.2 | 8.3, 17.7 |
≥3 (24) | 8.1 | 3.7, 14.4 | 6.6 | 3.2, 12.6 |
Mutationsa | ||||
Del 19b (232) | 19.3 | 15.6, 21.8 | 15.9 | 13.9, 19.1 |
L858Rb (162) | 14.5 | 12.7, 17.9 | 13.1 | 11.5, 15.2 |
Uc (84) | 7.4 | 5.7, 9.0 | 6.0 | 4.2, 8.1 |
ECOG PS, inc. mutations | ||||
0–1 (442)a | 15.8 | 14.4, 18.8 | 13.8 | 12.8, 15.2 |
Cb (364) | 18.2 | 15.5, 19.8 | 15.2 | 13.8, 17.7 |
U (77) | 7.4 | 5.7, 9.7 | 6.6 | 4.6, 8.2 |
2 (36) | 8.9 | 5.7, 13.2 | 6.2 | 2.5, 11.6 |
Cb (30) | 8.9 | 5.7, 13.9 | 7.7 | 3.9, 13.2 |
U (6) | 7.0 | 0.9, 13.0 | 1.4 | 0.4, 6.0 |
Brain metsa | ||||
No (395) | 15.8 | 14.1, 18.8 | 13.9 | 12.7, 15.5 |
Yes (83) | 13.7 | 9.7, 17.2 | 10.1 | 8.2, 13.9 |
Missing n = 1.
bDel 19/L858R only.
cIncludes, n (%): ex 20 ins: 37 (44).
Clinical trial identification
NCT01853826.
Editorial acknowledgement
Christina Jennings of GeoMed, an Ashfield company, part of UDG Healthcare plc.
Legal entity responsible for the study
Boehringer Ingelheim.
Funding
Boehringer Ingelheim.
Disclosure
F. De Marinis: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Advisory / Consultancy: Takeda; Research grant / Funding (institution): Boehringer Ingelheim. M. Hochmair: Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp & Dohme; Advisory / Consultancy: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: Pfizer. M.R. Migliorino: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: B.I.; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: ROCHE; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: PFIZER. G.Z. Mukhametshina: Advisory / Consultancy: Association of oncologists of Russian Federation; Full / Part-time employment: State Autonomous Healthcare Institution «Republican Clinical Oncology Dispensary of the Ministry of Health of the Republic of Tatarstan». M. Schumacher: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: AstraZeneca. S. Novello: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: BI; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: AbbVie; Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda. R. Dziadziuszko: Honoraria (self): Pfizer; Honoraria (self): Boehringer Ingelheim; Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: Roche; Honoraria (self): MSD; Honoraria (self): Bristol-Myers Squibb. W. Tang: Full / Part-time employment: Boehringer Ingelheim. L. Clementi: Full / Part-time employment: Boehringer Ingelheim Italia SpA. A. Cseh: Full / Part-time employment: Boehringer Ingelheim . All other authors have declared no conflicts of interest.
Resources from the same session
380P - Ventricular–Subventricular zone involvement: A predictive factor for survival in glioblastoma
Presenter: Vibhay Pareek
Session: Poster display session
Resources:
Abstract
381P - XKR8 is a promising potential prognostic marker in glioblastoma multiforme patients
Presenter: Kristina Havrysh
Session: Poster display session
Resources:
Abstract
383P - Screening of prognostic molecular biomarker for resectable pancreatic cancer
Presenter: Yonggang Peng
Session: Poster display session
Resources:
Abstract
384P - Prevalence of abnormal microsatellite instability test among ovary and endometrial cancer patients
Presenter: Min Kyu Kim
Session: Poster display session
Resources:
Abstract
385P - Identifying CASP8 polymorphisms associated with breast cancer risk in an Iranian population
Presenter: Alireza Pasdar
Session: Poster display session
Resources:
Abstract
386P - Unusual folding of NaPi2b transporter extramembrane domain 4 during malignant transformation
Presenter: Leysan Minigulova
Session: Poster display session
Resources:
Abstract
387P - 5-years conditional disease free survival and overall survival for breast cancer patients in South Korea
Presenter: Jee hyun Ahn
Session: Poster display session
Resources:
Abstract
388P - To identify circulating tumour cells by machine learning approach
Presenter: Yuebin Liang
Session: Poster display session
Resources:
Abstract
389P - The establishment of patient-derived organoid models and drug response of resectable non-small cell lung cancer
Presenter: Jing-Hua Chen
Session: Poster display session
Resources:
Abstract
395P - Filipinos and lung cancer: An infodemiological assessment using Google trends from 2009 to 2019
Presenter: Lance Isidore Catedral
Session: Poster display session
Resources:
Abstract