2653 - A combined analysis of two Phase IIIb studies of afatinib in EGFR TKI-naïve patients (pts) with EGFR mutation-positive (EGFRm+) NSCLC

Background

First-line afatinib significantly improved progression-free survival (PFS) in pts with EGFRm+ NSCLC compared with chemotherapy in LUX-Lung (LL) 3 and 6, and with gefitinib in LL7. However, in clinical practice, some EGFRm+ pts still receive chemotherapy as a first-line therapy. We report a combined analysis of data from two large, prospective, open-label, single-arm Phase IIIb studies of afatinib in pts with EGFR TKI-naïve NSCLC treated in a setting similar to real-world practice.

Methods

EGFR TKI-naïve pts with locally advanced/metastatic EGFRm+ NSCLC received 40 mg/day afatinib until progressive disease or lack of tolerability. Dose reduction to minimum 20 mg/day was permitted. Pts were enrolled across 8 European countries, Russia, Israel and Australia (study 1), and China, Hong Kong, India, Singapore and Taiwan (study 2). Time to symptomatic progression (TTSP), PFS, objective response and safety were analysed using interim (study 1; data cut-off 30 April 2018) and final (study 2; data cut-off 6 July 2018) data.

Results

A total of 1020 pts were treated: female: 59%; Asian/White: 54%/46%; median age: 61 years; ECOG PS 0/1/2: 26%/69%/5%; common/uncommon EGFR mutations: 82%/18%; treatment line 1/2/≥3: 69%/23%/8%; brain metastases: 18%. Median TTSP was 14.6 months (95% CI: 13.8–15.8); median PFS was 12.9 months (95% CI: 11.6–13.7). Objective response (OR) rate was 52.7%; median duration of OR was 12.9 months (95% CI: 11.7–13.8). Adverse events (AEs; any grade/grade ≥3) occurred in 1012/556 pts (99.2%/54.5%). Drug-related AEs (DRAEs; any grade/grade ≥3) occurred in 990/361 pts (97.1%/35.4%); most frequently (grade ≥3) diarrhoea (13.3%) and rash (9.2%). DRAEs leading to treatment discontinuation were reported in 54 pts (5.3%). AEs leading to dose reduction occurred in 412 patients (40.4%). Serious AEs occurred in 366 pts (35.9%).

Conclusions

In this combined analysis, safety data for afatinib were consistent with results from LL3, 6 and 7. Efficacy data were encouraging, with a median TTSP of 14.6 months. This analysis, which includes pts treated in later lines, and pts with ECOG PS 2, brain metastases, or uncommon mutations, suggests that afatinib has clinical benefit for pts in the real-world clinical setting.

Clinical trial identification

NCT01853826 and NCT01953913.

Editorial acknowledgement

Beth de Klerk, of GeoMed, an Ashfield company, part of UDG Healthcare plc.; supported financially by Boehringer Ingelheim.

Legal entity responsible for the study

Boehringer Ingelheim.

Funding

Boehringer Ingelheim.

Disclosure

F. de Marinis: Honoraria (self), Advisory / Consultancy: Roche; Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (institution), Research grant / Funding (self): Merck Sharp and Dohme; Research grant / Funding (self): Boehringer Ingelheim. A. Poltoratskiy: Advisory / Consultancy, Speaker Bureau / Expert testimony: GCP.center Russia. V. Lee: Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Merck Sharp and Dohme. D.M. Kowalski: Advisory / Consultancy: Boehringer Ingelheim. A. Passaro: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Merck Sharp and Dohme; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Roche; Advisory / Consultancy: Dako. L. Clementi: Full / Part-time employment: Boehringer Ingelheim Italia SpA. W. Tang: Full / Part-time employment: Boehringer Ingelheim. D.C. Huang: Full / Part-time employment: Boehringer Ingelheim (Taiwan Limited). A. Cseh: Full / Part-time employment: Boehringer Ingelheim; Shareholder / Stockholder / Stock options, Husband: Mylan. C. Zhou: Honoraria (self): Boehringer Ingelheim; Honoraria (self): Roche; Honoraria (self): Sanofi; Honoraria (self): Hengrui; Honoraria (self): Qilu; Honoraria (self): Merck Sharp and Dohme. Y. Wu: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Full / Part-time employment: Guangdong Provincial People’s Hospital, China; Honoraria (self): Eli Lilly; Honoraria (self): Pfizer; Honoraria (self), Research grant / Funding (self): Boehringer Ingelheim. All other authors have declared no conflicts of interest.