Abstract 2509
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%; 1st/2nd/≥3rd-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
Median TTSP, months (95% CI) | Median PFS, months (95% CI) | |
---|---|---|
All patients (n = 479) | 14.9 (13.8–17.6) | 13.4 (11.8–14.5) |
Line of therapy | ||
1st (n = 374) | 15.6 (14.1–18.5) | 13.8 (12.6–15.2) |
2nd (n = 81) | 14.7 (11.3–20.6) | 13.2 (8.3–17.7) |
≥3rd (n = 24) | 8.1 (3.7–14.4) | 6.6 (3.2–12.6) |
Baseline ECOG PS* | ||
0–1 (n = 442) | 15.8 (14.4–18.8) | 13.8 (12.8–15.2) |
2 (n = 36) | 8.9 (5.7–13.2) | 6.2 (2.5–11.6) |
Baseline EGFR mutation type* | ||
Common† (n = 416) | 15.9 (14.5–19.1) | 14.1 (13.0–15.7) |
Uncommon only‡ (n = 62) | 6.7 (5.4–8.3) | 5.9 (4.0–7.4) |
Baseline brain metastases* | ||
No (n = 395) | 15.8 (14.1–18.8) | 13.9 (12.7–15.5) |
Common§ (n = 326) | 17.9 (14.9–19.8) | 15.2 (13.8–17.7) |
Uncommon¶ (n = 69) | 6.7 (5.4–13.0) | 6.0 (4.0–8.1) |
Yes (n = 83) | 13.7 (9.7–17.2) | 10.1 (8.2–13.9) |
Common§ (n = 68) | 14.5 (11.6–19.1) | 11.6 (8.80–15.04) |
Uncommon¶ (n = 14) | 7.4 (3.3–9.7) | 5.9 (1.9–8.3) |
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.
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