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
481P - Updated survival outcomes of the phase II study of low starting dose of afatinib as first-line treatment in patients with EGFR mutation-positive non-small cell lung cancer (KTORG1402)
Presenter: Toshihide Yokoyama
Session: Poster display session
Resources:
Abstract
490P - Outcomes of sequential epidermal growth factor receptor tyrosine (EGFR) tyrosine kinase inhibitor (TKI) therapy in patients with advanced non-small cell lung carcinoma (NSCLC)- a real-world institutional experience
Presenter: Yvonne Ang
Session: Poster display session
Resources:
Abstract
498P - An observational retrospective study to evaluate the incidence of acquired EGFR T790M resistance in NSCLC patients with EGFR mutation following progression after at least one prior EGFR TKI treatment in Taiwan: ARISE study
Presenter: Shang-gin Wu
Session: Poster display session
Resources:
Abstract
501P - Clinical characteristics and efficacy in non-small cell lung cancer patients with EGFR exon 20 insertion and EGFR amplification
Presenter: Xin Gao
Session: Poster display session
Resources:
Abstract
502P - Epidermal growth factor receptor tyrosine kinase inhibitor treatment response in advanced non-small cell lung cancer with uncommon mutations: A multicenter observational study
Presenter: Masaki Kanazu
Session: Poster display session
Resources:
Abstract
483P - A phase IIIb, open-label study of afatinib in EGFR TKI-naïve patients with EGFR mutation-positive NSCLC: A biomarker analysis
Presenter: Rafael Rosell
Session: Poster display session
Resources:
Abstract
484P - Activity of afatinib in patients (pts) with EGFR mutation-positive (EGFRm+) NSCLC and baseline brain metastases: Pooled analysis of three large phase IIIb trials
Presenter: Maya Gottfried
Session: Poster display session
Resources:
Abstract
491P - Clinical outcomes of leptomeningeal metastases in EGFR-mutant lung adenocarcinoma
Presenter: Chia-I Shen
Session: Poster display session
Resources:
Abstract
510P - Paclitaxel as continuation maintenance therapy in patients with advanced non-small cell lung cancer
Presenter: Suzy Gohar
Session: Poster display session
Resources:
Abstract
496P - Higher osimertinib introduction rate achieved by multiple repeated re-biopsy after acquired resistance to first/second generation EGFR-TKIs
Presenter: Taira Ninomaru
Session: Poster display session
Resources:
Abstract