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Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial

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Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial. / Subbiah, Vivek; Kreitman, Robert J; Wainberg, Zev A; Gazzah, Anas; Lassen, Ulrik; Stein, Alexander; Wen, Patrick Y; Dietrich, Sascha; de Jonge, Maja J A; Blay, Jean-Yves; Italiano, Antoine; Yonemori, Kan; Cho, Daniel C; de Vos, Filip Y F L; Moreau, Philippe; Fernandez, Elena Elez; Schellens, Jan H M; Zielinski, Christoph C; Redhu, Suman; Boran, Aislyn; Passos, Vanessa Q; Ilankumaran, Palanichamy; Bang, Yung-Jue.

In: NAT MED, Vol. 29, No. 5, 05.2023, p. 1103-1112.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Subbiah, V, Kreitman, RJ, Wainberg, ZA, Gazzah, A, Lassen, U, Stein, A, Wen, PY, Dietrich, S, de Jonge, MJA, Blay, J-Y, Italiano, A, Yonemori, K, Cho, DC, de Vos, FYFL, Moreau, P, Fernandez, EE, Schellens, JHM, Zielinski, CC, Redhu, S, Boran, A, Passos, VQ, Ilankumaran, P & Bang, Y-J 2023, 'Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial', NAT MED, vol. 29, no. 5, pp. 1103-1112. https://doi.org/10.1038/s41591-023-02321-8

APA

Subbiah, V., Kreitman, R. J., Wainberg, Z. A., Gazzah, A., Lassen, U., Stein, A., Wen, P. Y., Dietrich, S., de Jonge, M. J. A., Blay, J-Y., Italiano, A., Yonemori, K., Cho, D. C., de Vos, F. Y. F. L., Moreau, P., Fernandez, E. E., Schellens, J. H. M., Zielinski, C. C., Redhu, S., ... Bang, Y-J. (2023). Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial. NAT MED, 29(5), 1103-1112. https://doi.org/10.1038/s41591-023-02321-8

Vancouver

Subbiah V, Kreitman RJ, Wainberg ZA, Gazzah A, Lassen U, Stein A et al. Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial. NAT MED. 2023 May;29(5):1103-1112. https://doi.org/10.1038/s41591-023-02321-8

Bibtex

@article{df8a3d4a193d493f8e712c602087b6cd,
title = "Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial",
abstract = "BRAFV600E alterations are prevalent across multiple tumors. Here we present final efficacy and safety results of a phase 2 basket trial of dabrafenib (BRAF kinase inhibitor) plus trametinib (MEK inhibitor) in eight cohorts of patients with BRAFV600E-mutated advanced rare cancers: anaplastic thyroid carcinoma (n = 36), biliary tract cancer (n = 43), gastrointestinal stromal tumor (n = 1), adenocarcinoma of the small intestine (n = 3), low-grade glioma (n = 13), high-grade glioma (n = 45), hairy cell leukemia (n = 55) and multiple myeloma (n = 19). The primary endpoint of investigator-assessed overall response rate in these cohorts was 56%, 53%, 0%, 67%, 54%, 33%, 89% and 50%, respectively. Secondary endpoints were median duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Median DoR was 14.4 months, 8.9 months, not reached, 7.7 months, not reached, 31.2 months, not reached and 11.1 months, respectively. Median PFS was 6.7 months, 9.0 months, not reached, not evaluable, 9.5 months, 5.5 months, not evaluable and 6.3 months, respectively. Median OS was 14.5 months, 13.5 months, not reached, 21.8 months, not evaluable, 17.6 months, not evaluable and 33.9 months, respectively. The most frequent (≥20% of patients) treatment-related adverse events were pyrexia (40.8%), fatigue (25.7%), chills (25.7%), nausea (23.8%) and rash (20.4%). The encouraging tumor-agnostic activity of dabrafenib plus trametinib suggests that this could be a promising treatment approach for some patients with BRAFV600E-mutated advanced rare cancers. ClinicalTrials.gov registration: NCT02034110 .",
author = "Vivek Subbiah and Kreitman, {Robert J} and Wainberg, {Zev A} and Anas Gazzah and Ulrik Lassen and Alexander Stein and Wen, {Patrick Y} and Sascha Dietrich and {de Jonge}, {Maja J A} and Jean-Yves Blay and Antoine Italiano and Kan Yonemori and Cho, {Daniel C} and {de Vos}, {Filip Y F L} and Philippe Moreau and Fernandez, {Elena Elez} and Schellens, {Jan H M} and Zielinski, {Christoph C} and Suman Redhu and Aislyn Boran and Passos, {Vanessa Q} and Palanichamy Ilankumaran and Yung-Jue Bang",
note = "{\textcopyright} 2023. The Author(s).",
year = "2023",
month = may,
doi = "10.1038/s41591-023-02321-8",
language = "English",
volume = "29",
pages = "1103--1112",
journal = "NAT MED",
issn = "1078-8956",
publisher = "NATURE PUBLISHING GROUP",
number = "5",

}

RIS

TY - JOUR

T1 - Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial

AU - Subbiah, Vivek

AU - Kreitman, Robert J

AU - Wainberg, Zev A

AU - Gazzah, Anas

AU - Lassen, Ulrik

AU - Stein, Alexander

AU - Wen, Patrick Y

AU - Dietrich, Sascha

AU - de Jonge, Maja J A

AU - Blay, Jean-Yves

AU - Italiano, Antoine

AU - Yonemori, Kan

AU - Cho, Daniel C

AU - de Vos, Filip Y F L

AU - Moreau, Philippe

AU - Fernandez, Elena Elez

AU - Schellens, Jan H M

AU - Zielinski, Christoph C

AU - Redhu, Suman

AU - Boran, Aislyn

AU - Passos, Vanessa Q

AU - Ilankumaran, Palanichamy

AU - Bang, Yung-Jue

N1 - © 2023. The Author(s).

PY - 2023/5

Y1 - 2023/5

N2 - BRAFV600E alterations are prevalent across multiple tumors. Here we present final efficacy and safety results of a phase 2 basket trial of dabrafenib (BRAF kinase inhibitor) plus trametinib (MEK inhibitor) in eight cohorts of patients with BRAFV600E-mutated advanced rare cancers: anaplastic thyroid carcinoma (n = 36), biliary tract cancer (n = 43), gastrointestinal stromal tumor (n = 1), adenocarcinoma of the small intestine (n = 3), low-grade glioma (n = 13), high-grade glioma (n = 45), hairy cell leukemia (n = 55) and multiple myeloma (n = 19). The primary endpoint of investigator-assessed overall response rate in these cohorts was 56%, 53%, 0%, 67%, 54%, 33%, 89% and 50%, respectively. Secondary endpoints were median duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Median DoR was 14.4 months, 8.9 months, not reached, 7.7 months, not reached, 31.2 months, not reached and 11.1 months, respectively. Median PFS was 6.7 months, 9.0 months, not reached, not evaluable, 9.5 months, 5.5 months, not evaluable and 6.3 months, respectively. Median OS was 14.5 months, 13.5 months, not reached, 21.8 months, not evaluable, 17.6 months, not evaluable and 33.9 months, respectively. The most frequent (≥20% of patients) treatment-related adverse events were pyrexia (40.8%), fatigue (25.7%), chills (25.7%), nausea (23.8%) and rash (20.4%). The encouraging tumor-agnostic activity of dabrafenib plus trametinib suggests that this could be a promising treatment approach for some patients with BRAFV600E-mutated advanced rare cancers. ClinicalTrials.gov registration: NCT02034110 .

AB - BRAFV600E alterations are prevalent across multiple tumors. Here we present final efficacy and safety results of a phase 2 basket trial of dabrafenib (BRAF kinase inhibitor) plus trametinib (MEK inhibitor) in eight cohorts of patients with BRAFV600E-mutated advanced rare cancers: anaplastic thyroid carcinoma (n = 36), biliary tract cancer (n = 43), gastrointestinal stromal tumor (n = 1), adenocarcinoma of the small intestine (n = 3), low-grade glioma (n = 13), high-grade glioma (n = 45), hairy cell leukemia (n = 55) and multiple myeloma (n = 19). The primary endpoint of investigator-assessed overall response rate in these cohorts was 56%, 53%, 0%, 67%, 54%, 33%, 89% and 50%, respectively. Secondary endpoints were median duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Median DoR was 14.4 months, 8.9 months, not reached, 7.7 months, not reached, 31.2 months, not reached and 11.1 months, respectively. Median PFS was 6.7 months, 9.0 months, not reached, not evaluable, 9.5 months, 5.5 months, not evaluable and 6.3 months, respectively. Median OS was 14.5 months, 13.5 months, not reached, 21.8 months, not evaluable, 17.6 months, not evaluable and 33.9 months, respectively. The most frequent (≥20% of patients) treatment-related adverse events were pyrexia (40.8%), fatigue (25.7%), chills (25.7%), nausea (23.8%) and rash (20.4%). The encouraging tumor-agnostic activity of dabrafenib plus trametinib suggests that this could be a promising treatment approach for some patients with BRAFV600E-mutated advanced rare cancers. ClinicalTrials.gov registration: NCT02034110 .

U2 - 10.1038/s41591-023-02321-8

DO - 10.1038/s41591-023-02321-8

M3 - SCORING: Journal article

C2 - 37059834

VL - 29

SP - 1103

EP - 1112

JO - NAT MED

JF - NAT MED

SN - 1078-8956

IS - 5

ER -