2509 - Afatinib in EGFR TKI-naïve patients with EGFR mutation-positive (EGFRm+) NSCLC: interim analysis of a Phase IIIb, multi-national, open-label study

Background

First-line afatinib demonstrated significantly improved PFS in patients with EGFRm+ NSCLC vs chemotherapy in LUX-Lung 3/6 (HR, 95% CI: 0.58, 0.43–0.78/0.28, 0.20–0.39) and vs gefitinib in LUX-Lung 7 (0.73, 0.57–0.95). Given the strict inclusion criteria of randomised controlled trials, it is important to support findings with evidence from real-world studies and broader patient populations. We report interim results of an open-label, Phase IIIb study of afatinib in the treatment of EGFRm+ NSCLC.

Methods

EGFR TKI-naïve patients with locally advanced/metastatic EGFRm+ NSCLC and ECOG PS 0–2 received afatinib 40 mg/day. Dose reduction was permitted (minimum 20 mg/day). Primary endpoint: adverse events (AEs; descriptive fashion). Efficacy was also assessed.

Results

A total of 479 patients were enrolled/treated (data cut-off 30 April 2018). Caucasian: 97%; 1^st/2^nd/≥3^rd-line therapy: 78%/17%/5%; ECOG PS 0–1/2: 92%/8%; common/uncommon only mutations: 87%/13%; brain metastases: 17%. Median time on afatinib was 359 days. Objective response/disease control rates were 46%/86%. Other efficacy outcomes are shown in Table. The most common grade ≥3 drug-related AEs (DRAEs) were, n (%): diarrhoea, 77 (16) and rash, 51 (11). 258 (54) patients had AEs leading to dose reduction (most commonly due to diarrhoea, 119 [25] or rash, 53 [11]) and 37 (8) had DRAEs leading to discontinuation (diarrhea, 16 [3]; all others, ≤4 [<1]). 39 (8) patients had serious DRAEs.Table:

1472P

Missing (n = 1)

Common (Del 19/L858R) mutations, with or without uncommon mutations

Uncommon mutations only, including, n (%, of those with uncommon mutations only): ex 20 ins, 37 (60); T790M, 12 (19); G719S/A/C, 12 (19); L861Q, 10 (16); S768I, 9 (15)

Del19-only or L858R-only mutations

Uncommon mutations, with or without common mutations CI, confidence interval; TTSP, time to symptomatic progression; PFS, progression-free survival

Conclusions

This interim analysis shows predictable and manageable safety, and encouraging efficacy with afatinib in a broad patient population with EGFRm+ NSCLC. Subgroup analyses showed encouraging PFS and TTSP, particularly for patients with Del19/L858R+ NSCLC regardless of brain metastases at baseline. The relatively high proportion of patients with tumours harbouring uncommon exon 20 insertions may account for differences in efficacy across common/uncommon mutation subgroups.

Clinical trial identification

NCT01853826.

Editorial acknowledgement

Laura Winton, 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; Research grant / Funding (self): Boehringer Ingelheim; Honoraria (institution), Research grant / Funding (self): Merck Sharp and Dohme. A. Poltoratskiy: Advisory / Consultancy, Speaker Bureau / Expert testimony: GCP.center Russia. M. Hochmair: Honoraria (self): AstraZeneca; Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Merck Sharp and Dohme; Advisory / Consultancy: Novartis; Honoraria (self): Pfizer; Honoraria (self), Advisory / Consultancy: Roche. A. Passaro: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Merck Sharp and Dohme; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Roche; Advisory / Consultancy: Dako. M.R. Migliorino: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Pfizer; 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: Merck Sharp and Dohme. 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: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Merck Sharp and Dohme; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; 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: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp and Dohme; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; 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. 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; Shareholder / Stockholder / Stock options, Husband: Mylan. D.M. Kowalski: Advisory / Consultancy: Boehringer Ingelheim. All other authors have declared no conflicts of interest.