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

doi:10.1016/S1470-2045(16)00077-2

Dabrafenib in patients with BRAF^V600E-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

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

338 Citations (Scopus)

Abstract

Background: Activating BRAF^V600E (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 BRAF^V600E mutation. Methods: In this phase 2, multicentre, non-randomised, open-label study, we enrolled previously treated and untreated patients with stage IV metastatic BRAF^V600E-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 BRAF^V600E-positive NSCLC. Our findings suggest that dabrafenib could represent a treatment option for a population of patients with limited therapeutic options. Funding: GlaxoSmithKline.

Original language	English
Pages (from-to)	642-650
Number of pages	9
Journal	The Lancet Oncology
Volume	17
Issue number	5
DOIs	https://doi.org/10.1016/S1470-2045(16)00077-2
Publication status	Published - 2016 May 1

Bibliographical note

Funding Information:
The funder was involved in the design of the study, data collection, data analysis, data interpretation, and writing of the report. Editorial support that did not involve writing was provided by ArticulateScience and funded by the sponsor. LP, CN, BMa, AD'A, BMo, and CMC had access to all the data in the study and the corresponding author had final responsibility for the decision to submit for publication.

Funding Information:
DP acts as an adviser for AstraZeneca, Boerhinger Ingelheim, Bristol-Myers Squibb, Lilly, MSD, Novartis, Pfizer, Pierre Fabre, and Roche. GR has received grants from GlaxoSmithKline and Novartis, acts as a consultant to Novartis and has received funding for research via his employer from Chugai/Roche, Millennium, and Pfizer. FB has received personal fees from GlaxoSmithKline and Novartis. P-JS has been involved in a clinical trial for GlaxoSmithKline. HJMG's institution has received payments from GlaxoSmithKline, MSD, Pfizer, and Roche. LP, CN, BMa, AD'A, BMo, and CMC were employees of GlaxoSmithKline during the study. CN, AD'A, and BMo have been or are currently employees of Novartis, and BMo owns stock in GlaxoSmithKline and Novartis. BEJ has received personal fees from AstraZeneca, Clovis Oncology, Genentech, Merck, and Novartis, honoraria from Chugai, and shares of post-market revenue for an EGFR genotyping patent. The other authors declare no competing interests.

Publisher Copyright:
© 2016 Elsevier Ltd.

All Science Journal Classification (ASJC) codes

Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/S1470-2045(16)00077-2

Cite this

Planchard, D., Kim, T. M., Mazieres, J., Quoix, E., Riely, G., Barlesi, F., Souquet, P. J., Smit, E. F., Groen, H. J. M., Kelly, R. J., Cho, B. C., Socinski, M. A., Pandite, L., Nase, C., Ma, B., D'Amelio, A., Mookerjee, B., Curtis, C. M., & Johnson, B. E. (2016). Dabrafenib in patients with BRAF^V600E-positive advanced non-small-cell lung cancer: A single-arm, multicentre, open-label, phase 2 trial. The Lancet Oncology, 17(5), 642-650. https://doi.org/10.1016/S1470-2045(16)00077-2

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

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.}",

note = "Funding Information: The funder was involved in the design of the study, data collection, data analysis, data interpretation, and writing of the report. Editorial support that did not involve writing was provided by ArticulateScience and funded by the sponsor. LP, CN, BMa, AD'A, BMo, and CMC had access to all the data in the study and the corresponding author had final responsibility for the decision to submit for publication. Funding Information: DP acts as an adviser for AstraZeneca, Boerhinger Ingelheim, Bristol-Myers Squibb, Lilly, MSD, Novartis, Pfizer, Pierre Fabre, and Roche. GR has received grants from GlaxoSmithKline and Novartis, acts as a consultant to Novartis and has received funding for research via his employer from Chugai/Roche, Millennium, and Pfizer. FB has received personal fees from GlaxoSmithKline and Novartis. P-JS has been involved in a clinical trial for GlaxoSmithKline. HJMG's institution has received payments from GlaxoSmithKline, MSD, Pfizer, and Roche. LP, CN, BMa, AD'A, BMo, and CMC were employees of GlaxoSmithKline during the study. CN, AD'A, and BMo have been or are currently employees of Novartis, and BMo owns stock in GlaxoSmithKline and Novartis. BEJ has received personal fees from AstraZeneca, Clovis Oncology, Genentech, Merck, and Novartis, honoraria from Chugai, and shares of post-market revenue for an EGFR genotyping patent. The other authors declare no competing interests. Publisher Copyright: {\textcopyright} 2016 Elsevier Ltd.",

year = "2016",

month = may,

day = "1",

doi = "10.1016/S1470-2045(16)00077-2",

language = "English",

volume = "17",

pages = "642--650",

journal = "The Lancet Oncology",

issn = "1470-2045",

publisher = "Lancet Publishing Group",

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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 BRAF^V600E-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

TY - JOUR

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.

N1 - Funding Information: The funder was involved in the design of the study, data collection, data analysis, data interpretation, and writing of the report. Editorial support that did not involve writing was provided by ArticulateScience and funded by the sponsor. LP, CN, BMa, AD'A, BMo, and CMC had access to all the data in the study and the corresponding author had final responsibility for the decision to submit for publication. Funding Information: DP acts as an adviser for AstraZeneca, Boerhinger Ingelheim, Bristol-Myers Squibb, Lilly, MSD, Novartis, Pfizer, Pierre Fabre, and Roche. GR has received grants from GlaxoSmithKline and Novartis, acts as a consultant to Novartis and has received funding for research via his employer from Chugai/Roche, Millennium, and Pfizer. FB has received personal fees from GlaxoSmithKline and Novartis. P-JS has been involved in a clinical trial for GlaxoSmithKline. HJMG's institution has received payments from GlaxoSmithKline, MSD, Pfizer, and Roche. LP, CN, BMa, AD'A, BMo, and CMC were employees of GlaxoSmithKline during the study. CN, AD'A, and BMo have been or are currently employees of Novartis, and BMo owns stock in GlaxoSmithKline and Novartis. BEJ has received personal fees from AstraZeneca, Clovis Oncology, Genentech, Merck, and Novartis, honoraria from Chugai, and shares of post-market revenue for an EGFR genotyping patent. The other authors declare no competing interests. Publisher Copyright: © 2016 Elsevier Ltd.

PY - 2016/5/1

Y1 - 2016/5/1

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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