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Poster Display session 1

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

Date

28 Sep 2019

Session

Poster Display session 1

Topics

Tumour Site

Non-Small Cell Lung Cancer

Presenters

Filippo de Marinis

Citation

Annals of Oncology (2019) 30 (suppl_5): v591-v601. 10.1093/annonc/mdz259

Authors

F. de Marinis1, K.K. Laktionov2, A. Poltoratskiy3, I. Egorova4, M. Hochmair5, A. Passaro1, M.R. Migliorino6, G. Metro7, M. Gottfried8, D. Tsoi9, G. Ostoros10, S. Rizzato11, G.Z. Mukhametshina12, M. Schumacher13, S. Novello14, W. Tang15, L. Clementi16, A. Cseh17, D.M. Kowalski18

Author affiliations

  • 1 Division Of Thoracic Oncology, European Institute of Oncology, 20141 - Milan/IT
  • 2 Carcinogenesis Institute Of N.n Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, 119991 - Moscow/RU
  • 3 Department Of Preclinical And Clinical Trials, Petrov Research Institute of Oncology, St Petersburg/RU
  • 4 Thoracic Department, Clinical Oncology Dispensary, St Petersburg/RU
  • 5 Respiratory Oncology Unit, Otto Wagner Hospital, Vienna/AT
  • 6 Department Of Oncological Pneumology, San Camillo-Forlanini Hospital, Rome/IT
  • 7 Department Of Medical Oncology, Santa Maria della Misericordia Hospital, Perugia/IT
  • 8 Department Of Oncology, Tel Aviv University, Tel Aviv/IL
  • 9 Department Of Oncology, St John of God Murdoch Hospital, Murdoch/AU
  • 10 Department Of Tumor Biology, National Korányi Institute for Pulmonology, Budapest/HU
  • 11 Department Of Oncology, Azienda Sanitaria-Universitaria Integrata, Udine/IT
  • 12 State Healthcare Institute Republican Clinical Oncological Center, Ministry of Health of the Republic of Tatarstan, Kazan/RU
  • 13 Thoracic Centre, Ordensklinikum Elisabethinen, Linz/AT
  • 14 Oncology Department, University of Turin, Turin/IT
  • 15 Statistics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield/US
  • 16 Clinical Operations, Boehringer Ingelheim Italia S.p.A., Milan/IT
  • 17 Department Of Medical Affairs, Boehringer Ingelheim RCV GmbH & Co. KG, Vienna/AT
  • 18 Department Of Lung Cancer And Thoracic Oncology, Oncology Centre and Institute, 02-781 - Warsaw/PL

Resources

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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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