Dabrafenib in patients with BRAFV600E-positive advanced non-small-cell lung cancer: A single-arm, multicentre, open-label, phase 2 trial

David Planchard, Tae Min Kim, Julien Mazieres, Elisabeth Quoix, Gregory Riely, Fabrice Barlesi, Pierre Jean Souquet, Egbert F. Smit, Harry J.M. Groen, Ronan J. Kelly, B. C. Cho, Mark A. Socinski, Lini Pandite, Christine Nase, Bo Ma, Anthony D'Amelio, Bijoyesh Mookerjee, C. Martin Curtis, Bruce E. Johnson

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Abstract

Background: Activating BRAFV600E (Val600Glu) mutations are found in about 1-2% of lung adenocarcinomas, which might provide an opportunity for targeted treatment in these patients. Dabrafenib is an oral selective inhibitor of BRAF kinase. We did a trial to assess the clinical activity of dabrafenib in patients with advanced non-small-cell lung cancer (NSCLC) positive for the BRAFV600E mutation. Methods: In this phase 2, multicentre, non-randomised, open-label study, we enrolled previously treated and untreated patients with stage IV metastatic BRAFV600E-positive NSCLC. Patients received oral dabrafenib 150 mg twice daily. The primary endpoint was investigator-assessed overall response, which was assessed in patients who had received at least one dose of dabrafenib; safety was also assessed in this population. The study is ongoing but not enrolling patients in this cohort. This trial is registered with ClinicalTrials.gov, number NCT01336634. Findings: Between Aug 3, 2011, and Feb 25, 2014, 84 patients were enrolled, six of whom had not previously received systemic treatment for NSCLC. 26 of the 78 previously treated patients achieved an investigator-assessed overall response (33% [95% CI 23-45]). Four of the six previously untreated patients had an objective response. One patient died from an intracranial haemorrhage that was judged by the investigator to be due to the study drug. Serious adverse events were reported in 35 (42%) of 84 patients. The most frequent grade 3 or worse adverse events were cutaneous squamous-cell carcinoma in ten (12%), asthenia in four (5%), and basal-cell carcinoma in four (5%). Interpretation: Dabrafenib showed clinical activity in BRAFV600E-positive NSCLC. Our findings suggest that dabrafenib could represent a treatment option for a population of patients with limited therapeutic options. Funding: GlaxoSmithKline.

Original languageEnglish
Pages (from-to)642-650
Number of pages9
JournalThe Lancet Oncology
Volume17
Issue number5
DOIs
Publication statusPublished - 2016 May 1

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Non-Small Cell Lung Carcinoma
Research Personnel
dabrafenib
Proto-Oncogene Proteins B-raf
Asthenia
Mutation
Intracranial Hemorrhages
Basal Cell Carcinoma
Therapeutics
Population
Squamous Cell Carcinoma
Safety
Skin

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Planchard, David ; Kim, Tae Min ; Mazieres, Julien ; Quoix, Elisabeth ; Riely, Gregory ; Barlesi, Fabrice ; Souquet, Pierre Jean ; Smit, Egbert F. ; Groen, Harry J.M. ; Kelly, Ronan J. ; Cho, B. C. ; Socinski, Mark A. ; Pandite, Lini ; Nase, Christine ; Ma, Bo ; D'Amelio, Anthony ; Mookerjee, Bijoyesh ; Curtis, C. Martin ; Johnson, Bruce E. / Dabrafenib in patients with BRAFV600E-positive advanced non-small-cell lung cancer : A single-arm, multicentre, open-label, phase 2 trial. In: The Lancet Oncology. 2016 ; Vol. 17, No. 5. pp. 642-650.
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abstract = "Background: Activating BRAFV600E (Val600Glu) mutations are found in about 1-2{\%} of lung adenocarcinomas, which might provide an opportunity for targeted treatment in these patients. Dabrafenib is an oral selective inhibitor of BRAF kinase. We did a trial to assess the clinical activity of dabrafenib in patients with advanced non-small-cell lung cancer (NSCLC) positive for the BRAFV600E mutation. Methods: In this phase 2, multicentre, non-randomised, open-label study, we enrolled previously treated and untreated patients with stage IV metastatic BRAFV600E-positive NSCLC. Patients received oral dabrafenib 150 mg twice daily. The primary endpoint was investigator-assessed overall response, which was assessed in patients who had received at least one dose of dabrafenib; safety was also assessed in this population. The study is ongoing but not enrolling patients in this cohort. This trial is registered with ClinicalTrials.gov, number NCT01336634. Findings: Between Aug 3, 2011, and Feb 25, 2014, 84 patients were enrolled, six of whom had not previously received systemic treatment for NSCLC. 26 of the 78 previously treated patients achieved an investigator-assessed overall response (33{\%} [95{\%} CI 23-45]). Four of the six previously untreated patients had an objective response. One patient died from an intracranial haemorrhage that was judged by the investigator to be due to the study drug. Serious adverse events were reported in 35 (42{\%}) of 84 patients. The most frequent grade 3 or worse adverse events were cutaneous squamous-cell carcinoma in ten (12{\%}), asthenia in four (5{\%}), and basal-cell carcinoma in four (5{\%}). Interpretation: Dabrafenib showed clinical activity in BRAFV600E-positive NSCLC. Our findings suggest that dabrafenib could represent a treatment option for a population of patients with limited therapeutic options. Funding: GlaxoSmithKline.",
author = "David Planchard and Kim, {Tae Min} and Julien Mazieres and Elisabeth Quoix and Gregory Riely and Fabrice Barlesi and Souquet, {Pierre Jean} and Smit, {Egbert F.} and Groen, {Harry J.M.} and Kelly, {Ronan J.} and Cho, {B. C.} and Socinski, {Mark A.} and Lini Pandite and Christine Nase and Bo Ma and Anthony D'Amelio and Bijoyesh Mookerjee and Curtis, {C. Martin} and Johnson, {Bruce E.}",
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Planchard, D, Kim, TM, Mazieres, J, Quoix, E, Riely, G, Barlesi, F, Souquet, PJ, Smit, EF, Groen, HJM, Kelly, RJ, Cho, BC, Socinski, MA, Pandite, L, Nase, C, Ma, B, D'Amelio, A, Mookerjee, B, Curtis, CM & Johnson, BE 2016, 'Dabrafenib in patients with BRAFV600E-positive advanced non-small-cell lung cancer: A single-arm, multicentre, open-label, phase 2 trial', The Lancet Oncology, vol. 17, no. 5, pp. 642-650. https://doi.org/10.1016/S1470-2045(16)00077-2

Dabrafenib in patients with BRAFV600E-positive advanced non-small-cell lung cancer : A single-arm, multicentre, open-label, phase 2 trial. / Planchard, David; Kim, Tae Min; Mazieres, Julien; Quoix, Elisabeth; Riely, Gregory; Barlesi, Fabrice; Souquet, Pierre Jean; Smit, Egbert F.; Groen, Harry J.M.; Kelly, Ronan J.; Cho, B. C.; Socinski, Mark A.; Pandite, Lini; Nase, Christine; Ma, Bo; D'Amelio, Anthony; Mookerjee, Bijoyesh; Curtis, C. Martin; Johnson, Bruce E.

In: The Lancet Oncology, Vol. 17, No. 5, 01.05.2016, p. 642-650.

Research output: Contribution to journalArticle

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T1 - Dabrafenib in patients with BRAFV600E-positive advanced non-small-cell lung cancer

T2 - A single-arm, multicentre, open-label, phase 2 trial

AU - Planchard, David

AU - Kim, Tae Min

AU - Mazieres, Julien

AU - Quoix, Elisabeth

AU - Riely, Gregory

AU - Barlesi, Fabrice

AU - Souquet, Pierre Jean

AU - Smit, Egbert F.

AU - Groen, Harry J.M.

AU - Kelly, Ronan J.

AU - Cho, B. C.

AU - Socinski, Mark A.

AU - Pandite, Lini

AU - Nase, Christine

AU - Ma, Bo

AU - D'Amelio, Anthony

AU - Mookerjee, Bijoyesh

AU - Curtis, C. Martin

AU - Johnson, Bruce E.

PY - 2016/5/1

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N2 - Background: Activating BRAFV600E (Val600Glu) mutations are found in about 1-2% of lung adenocarcinomas, which might provide an opportunity for targeted treatment in these patients. Dabrafenib is an oral selective inhibitor of BRAF kinase. We did a trial to assess the clinical activity of dabrafenib in patients with advanced non-small-cell lung cancer (NSCLC) positive for the BRAFV600E mutation. Methods: In this phase 2, multicentre, non-randomised, open-label study, we enrolled previously treated and untreated patients with stage IV metastatic BRAFV600E-positive NSCLC. Patients received oral dabrafenib 150 mg twice daily. The primary endpoint was investigator-assessed overall response, which was assessed in patients who had received at least one dose of dabrafenib; safety was also assessed in this population. The study is ongoing but not enrolling patients in this cohort. This trial is registered with ClinicalTrials.gov, number NCT01336634. Findings: Between Aug 3, 2011, and Feb 25, 2014, 84 patients were enrolled, six of whom had not previously received systemic treatment for NSCLC. 26 of the 78 previously treated patients achieved an investigator-assessed overall response (33% [95% CI 23-45]). Four of the six previously untreated patients had an objective response. One patient died from an intracranial haemorrhage that was judged by the investigator to be due to the study drug. Serious adverse events were reported in 35 (42%) of 84 patients. The most frequent grade 3 or worse adverse events were cutaneous squamous-cell carcinoma in ten (12%), asthenia in four (5%), and basal-cell carcinoma in four (5%). Interpretation: Dabrafenib showed clinical activity in BRAFV600E-positive NSCLC. Our findings suggest that dabrafenib could represent a treatment option for a population of patients with limited therapeutic options. Funding: GlaxoSmithKline.

AB - Background: Activating BRAFV600E (Val600Glu) mutations are found in about 1-2% of lung adenocarcinomas, which might provide an opportunity for targeted treatment in these patients. Dabrafenib is an oral selective inhibitor of BRAF kinase. We did a trial to assess the clinical activity of dabrafenib in patients with advanced non-small-cell lung cancer (NSCLC) positive for the BRAFV600E mutation. Methods: In this phase 2, multicentre, non-randomised, open-label study, we enrolled previously treated and untreated patients with stage IV metastatic BRAFV600E-positive NSCLC. Patients received oral dabrafenib 150 mg twice daily. The primary endpoint was investigator-assessed overall response, which was assessed in patients who had received at least one dose of dabrafenib; safety was also assessed in this population. The study is ongoing but not enrolling patients in this cohort. This trial is registered with ClinicalTrials.gov, number NCT01336634. Findings: Between Aug 3, 2011, and Feb 25, 2014, 84 patients were enrolled, six of whom had not previously received systemic treatment for NSCLC. 26 of the 78 previously treated patients achieved an investigator-assessed overall response (33% [95% CI 23-45]). Four of the six previously untreated patients had an objective response. One patient died from an intracranial haemorrhage that was judged by the investigator to be due to the study drug. Serious adverse events were reported in 35 (42%) of 84 patients. The most frequent grade 3 or worse adverse events were cutaneous squamous-cell carcinoma in ten (12%), asthenia in four (5%), and basal-cell carcinoma in four (5%). Interpretation: Dabrafenib showed clinical activity in BRAFV600E-positive NSCLC. Our findings suggest that dabrafenib could represent a treatment option for a population of patients with limited therapeutic options. Funding: GlaxoSmithKline.

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