Afatinib in NSCLC With HER2 Mutations: Results of the Prospective, Open-Label Phase II NICHE Trial of European Thoracic Oncology Platform (ETOP)

Rafal Dziadziuszko, Egbert F. Smit, Urania Dafni, Juergen Wolf, Bartosz Wasąg, Wojciech Biernat, Stephen P. Finn, Roswitha Kammler, Zoi Tsourti, Manuela Rabaglio, Barbara Ruepp, Heidi Roschitzki-Voser, Rolf A. Stahel, Enriqueta Felip, Solange Peters

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Introduction: Mutations in erb-b2 receptor tyrosine kinase 2 (HER2) oncogene are observed in approximately 3% of lung adenocarcinomas or mixed tumors with adenocarcinoma component. Activity of various biologically distinct HER2 inhibitors, including the pan-HER inhibitor afatinib, has been reported in several retrospective trials or small series in advanced pretreated NSCLC with HER2 mutations. We report the first prospective evaluation of afatinib for the treatment of this molecularly defined entity. Methods: NICHE, a single-arm phase II trial using a two-stage Simon's design, explored the potential of afatinib to control disease in pretreated patients with advanced NSCLC harboring HER2 exon 20 mutations. A total of 13 patients entered the trial and were treated with afatinib 40 mg/day until tumor progression or lack of tolerability. Results: The first-stage stopping boundary was crossed when five of nine patients did not achieve disease control at 12 weeks. The accrual into the trial was stopped with total 13 patients enrolled, with 7 (53.8%) achieving disease control at 12 weeks. Except for 1 patient with early death, progression was documented for all patients, with median progression-free survival of 15.9 weeks (95% confidence interval: 6.0–35.4), and median overall survival of 56.0 weeks (95% confidence interval: 16.3– upper limit not estimable). The toxicity profile was in the expected range. Conclusions: Afatinib did not show the expected potential for disease control in NSCLC. However, more than half of the patients in the full cohort achieved disease control at 12 weeks.
Original languageEnglish
JournalJournal of Thoracic Oncology
DOIs
Publication statusPublished - 2019

Cite this

Dziadziuszko, Rafal ; Smit, Egbert F. ; Dafni, Urania ; Wolf, Juergen ; Wasąg, Bartosz ; Biernat, Wojciech ; Finn, Stephen P. ; Kammler, Roswitha ; Tsourti, Zoi ; Rabaglio, Manuela ; Ruepp, Barbara ; Roschitzki-Voser, Heidi ; Stahel, Rolf A. ; Felip, Enriqueta ; Peters, Solange. / Afatinib in NSCLC With HER2 Mutations: Results of the Prospective, Open-Label Phase II NICHE Trial of European Thoracic Oncology Platform (ETOP). In: Journal of Thoracic Oncology. 2019.
@article{078b83ccf9da4eff852fc47a40492f4f,
title = "Afatinib in NSCLC With HER2 Mutations: Results of the Prospective, Open-Label Phase II NICHE Trial of European Thoracic Oncology Platform (ETOP)",
abstract = "Introduction: Mutations in erb-b2 receptor tyrosine kinase 2 (HER2) oncogene are observed in approximately 3{\%} of lung adenocarcinomas or mixed tumors with adenocarcinoma component. Activity of various biologically distinct HER2 inhibitors, including the pan-HER inhibitor afatinib, has been reported in several retrospective trials or small series in advanced pretreated NSCLC with HER2 mutations. We report the first prospective evaluation of afatinib for the treatment of this molecularly defined entity. Methods: NICHE, a single-arm phase II trial using a two-stage Simon's design, explored the potential of afatinib to control disease in pretreated patients with advanced NSCLC harboring HER2 exon 20 mutations. A total of 13 patients entered the trial and were treated with afatinib 40 mg/day until tumor progression or lack of tolerability. Results: The first-stage stopping boundary was crossed when five of nine patients did not achieve disease control at 12 weeks. The accrual into the trial was stopped with total 13 patients enrolled, with 7 (53.8{\%}) achieving disease control at 12 weeks. Except for 1 patient with early death, progression was documented for all patients, with median progression-free survival of 15.9 weeks (95{\%} confidence interval: 6.0–35.4), and median overall survival of 56.0 weeks (95{\%} confidence interval: 16.3– upper limit not estimable). The toxicity profile was in the expected range. Conclusions: Afatinib did not show the expected potential for disease control in NSCLC. However, more than half of the patients in the full cohort achieved disease control at 12 weeks.",
author = "Rafal Dziadziuszko and Smit, {Egbert F.} and Urania Dafni and Juergen Wolf and Bartosz Wasąg and Wojciech Biernat and Finn, {Stephen P.} and Roswitha Kammler and Zoi Tsourti and Manuela Rabaglio and Barbara Ruepp and Heidi Roschitzki-Voser and Stahel, {Rolf A.} and Enriqueta Felip and Solange Peters",
year = "2019",
doi = "10.1016/j.jtho.2019.02.017",
language = "English",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "International Association for the Study of Lung Cancer",

}

Dziadziuszko, R, Smit, EF, Dafni, U, Wolf, J, Wasąg, B, Biernat, W, Finn, SP, Kammler, R, Tsourti, Z, Rabaglio, M, Ruepp, B, Roschitzki-Voser, H, Stahel, RA, Felip, E & Peters, S 2019, 'Afatinib in NSCLC With HER2 Mutations: Results of the Prospective, Open-Label Phase II NICHE Trial of European Thoracic Oncology Platform (ETOP)' Journal of Thoracic Oncology. https://doi.org/10.1016/j.jtho.2019.02.017

Afatinib in NSCLC With HER2 Mutations: Results of the Prospective, Open-Label Phase II NICHE Trial of European Thoracic Oncology Platform (ETOP). / Dziadziuszko, Rafal; Smit, Egbert F.; Dafni, Urania; Wolf, Juergen; Wasąg, Bartosz; Biernat, Wojciech; Finn, Stephen P.; Kammler, Roswitha; Tsourti, Zoi; Rabaglio, Manuela; Ruepp, Barbara; Roschitzki-Voser, Heidi; Stahel, Rolf A.; Felip, Enriqueta; Peters, Solange.

In: Journal of Thoracic Oncology, 2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Afatinib in NSCLC With HER2 Mutations: Results of the Prospective, Open-Label Phase II NICHE Trial of European Thoracic Oncology Platform (ETOP)

AU - Dziadziuszko, Rafal

AU - Smit, Egbert F.

AU - Dafni, Urania

AU - Wolf, Juergen

AU - Wasąg, Bartosz

AU - Biernat, Wojciech

AU - Finn, Stephen P.

AU - Kammler, Roswitha

AU - Tsourti, Zoi

AU - Rabaglio, Manuela

AU - Ruepp, Barbara

AU - Roschitzki-Voser, Heidi

AU - Stahel, Rolf A.

AU - Felip, Enriqueta

AU - Peters, Solange

PY - 2019

Y1 - 2019

N2 - Introduction: Mutations in erb-b2 receptor tyrosine kinase 2 (HER2) oncogene are observed in approximately 3% of lung adenocarcinomas or mixed tumors with adenocarcinoma component. Activity of various biologically distinct HER2 inhibitors, including the pan-HER inhibitor afatinib, has been reported in several retrospective trials or small series in advanced pretreated NSCLC with HER2 mutations. We report the first prospective evaluation of afatinib for the treatment of this molecularly defined entity. Methods: NICHE, a single-arm phase II trial using a two-stage Simon's design, explored the potential of afatinib to control disease in pretreated patients with advanced NSCLC harboring HER2 exon 20 mutations. A total of 13 patients entered the trial and were treated with afatinib 40 mg/day until tumor progression or lack of tolerability. Results: The first-stage stopping boundary was crossed when five of nine patients did not achieve disease control at 12 weeks. The accrual into the trial was stopped with total 13 patients enrolled, with 7 (53.8%) achieving disease control at 12 weeks. Except for 1 patient with early death, progression was documented for all patients, with median progression-free survival of 15.9 weeks (95% confidence interval: 6.0–35.4), and median overall survival of 56.0 weeks (95% confidence interval: 16.3– upper limit not estimable). The toxicity profile was in the expected range. Conclusions: Afatinib did not show the expected potential for disease control in NSCLC. However, more than half of the patients in the full cohort achieved disease control at 12 weeks.

AB - Introduction: Mutations in erb-b2 receptor tyrosine kinase 2 (HER2) oncogene are observed in approximately 3% of lung adenocarcinomas or mixed tumors with adenocarcinoma component. Activity of various biologically distinct HER2 inhibitors, including the pan-HER inhibitor afatinib, has been reported in several retrospective trials or small series in advanced pretreated NSCLC with HER2 mutations. We report the first prospective evaluation of afatinib for the treatment of this molecularly defined entity. Methods: NICHE, a single-arm phase II trial using a two-stage Simon's design, explored the potential of afatinib to control disease in pretreated patients with advanced NSCLC harboring HER2 exon 20 mutations. A total of 13 patients entered the trial and were treated with afatinib 40 mg/day until tumor progression or lack of tolerability. Results: The first-stage stopping boundary was crossed when five of nine patients did not achieve disease control at 12 weeks. The accrual into the trial was stopped with total 13 patients enrolled, with 7 (53.8%) achieving disease control at 12 weeks. Except for 1 patient with early death, progression was documented for all patients, with median progression-free survival of 15.9 weeks (95% confidence interval: 6.0–35.4), and median overall survival of 56.0 weeks (95% confidence interval: 16.3– upper limit not estimable). The toxicity profile was in the expected range. Conclusions: Afatinib did not show the expected potential for disease control in NSCLC. However, more than half of the patients in the full cohort achieved disease control at 12 weeks.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85064241343&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/30825613

U2 - 10.1016/j.jtho.2019.02.017

DO - 10.1016/j.jtho.2019.02.017

M3 - Article

JO - Journal of Thoracic Oncology

JF - Journal of Thoracic Oncology

SN - 1556-0864

ER -