482P - Interim analysis from a phase IIIb, open-label study of afatinib in EGFR TKI-naïve patients (pts) with EGFR mutation-positive (EGFRm+) NSCLC

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%; 1^st/2^nd/≥3^rd-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

Missing n = 1.

Del 19/L858R only.

Includes, 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.