Break-MB: a phase II study assessing overall intracranial response rate (OIRR) to dabrafenib (GSK2118436) in patients (pts) with BRAF V600E/k mutation-positive melanoma with brain metastases (mets)

John M. Kirkwood; Georgina V. Long; Uwe Trefzer; Michael A. Davies; Paolo Antonio Ascierto; Paul B. Chapman; Igor Puzanov; Axel Hauschild; Caroline Robert; Richard Kefford; Vicki L. Goodman; Julie C. Switzky; R. Suzanne Swann; Anne-Marie Martin; Mary E. Guckert; Michael R. W. Streit; Dirk Schadendorf

doi:10.1200/jco.2012.30.15_suppl.8501

Abstract

Background: Melanoma brain mets carry a poor prognosis (median survival ≤4 months), for which more effective therapies are needed. Dabrafenib is a potent, selective oral inhibitor of mutated BRAF that has demonstrated clinical efficacy in pts with BRAF V600E/K mutant melanoma and previously untreated brain mets in a phase I study. Therefore, a phase II study (BREAK-MB) was initiated.

Methods: Stage IV pts with ≥ 1 intracranial met (0.5 cm–4 cm assessed by MRI) without prior brain therapy (Cohort A) or with progression following prior brain therapy (Cohort B) were eligible with V600E/K mutation. Pts received dabrafenib 150 mg BID. The primary endpoint was investigator-assessed OIRR among V600E mutation-positive pts.

Results: Overall, 172 pts were recruited. At interim analysis, of 127 pts enrolled (safety population), 41 (Cohort A n=24; Cohort B n=17) had reached 8-week disease assessment. Unconfirmed OIRR in Cohort A was 10/19, (53%; 95% CI: 28.9–75.6%) for V600E and 1/5 (20%; 95% CI: 0.5–71.6%) for V600K pts. In Cohort B unconfirmed OIRR was 8/15 (53%; 95% CI: 26.6%–78.7%) for V600E and 1/2 (50%; 95% CI: 1.3–98.7%) for V600K pts. Unconfirmed overall response rate (ORR) in Cohort A was 10/19 (53%; 95% CI: 28.9–75.6%) for V600E and 1/5 (20%; 95% CI: 0.5–71.6%) for V600K pts. In Cohort B unconfirmed ORR was 6/15 (40%; 95% CI: 16.3–67.7%) for V600E and 1/2 (50%; 95% CI: 1.3–98.7%) for V600K pts. In the safety population, 12/63 pts (19%) in Cohort A reported an SAE; 1 (2%) was fatal (cerebral hemorrhage). In Cohort B 15/64 pts (25%) reported an SAE; 1 (2%) was fatal (seizure). In Cohort A, 47 pts (75%) experienced AEs: 9 grade 3 (14%) and 3 grade 4 (5%). The most common AEs were headache (21%), hyperkeratosis and rash (17% each). In Cohort B, 47 pts (73%) experienced AEs: 12 grade 3 (19%) and 3 grade 4 (5%). The most common AEs were fatigue or nausea (22% each) and pyrexia (17%).

Conclusions: Dabrafenib shows high clinical activity both in pts with intra- and extracranial mets with acceptable toxicity. Final data will be presented.

Original language	English
Pages (from-to)	8501-8501
Number of pages	1
Journal	Journal of Clinical Oncology
Volume	30
Issue number	Supplement 15
DOIs	https://doi.org/10.1200/jco.2012.30.15_suppl.8501
Publication status	Published - 20 May 2012
Externally published	Yes
Event	48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) - Chicago, United States Duration: 1 Jun 2012 → 6 Jun 2012

Access to Document

10.1200/jco.2012.30.15_suppl.8501

http://meetinglibrary.asco.org/content/97727-114

Cite this

Kirkwood, J. M., Long, G. V., Trefzer, U., Davies, M. A., Ascierto, P. A., Chapman, P. B., Puzanov, I., Hauschild, A., Robert, C., Kefford, R., Goodman, V. L., Switzky, J. C., Swann, R. S., Martin, A.-M., Guckert, M. E., Streit, M. R. W., & Schadendorf, D. (2012). Break-MB: a phase II study assessing overall intracranial response rate (OIRR) to dabrafenib (GSK2118436) in patients (pts) with BRAF V600E/k mutation-positive melanoma with brain metastases (mets). Journal of Clinical Oncology, 30(Supplement 15), 8501-8501. https://doi.org/10.1200/jco.2012.30.15_suppl.8501

@article{77a4bbda34304b6d8fffeb3987a80de6,

title = "Break-MB: a phase II study assessing overall intracranial response rate (OIRR) to dabrafenib (GSK2118436) in patients (pts) with BRAF V600E/k mutation-positive melanoma with brain metastases (mets)",

abstract = "Background: Melanoma brain mets carry a poor prognosis (median survival ≤4 months), for which more effective therapies are needed. Dabrafenib is a potent, selective oral inhibitor of mutated BRAF that has demonstrated clinical efficacy in pts with BRAF V600E/K mutant melanoma and previously untreated brain mets in a phase I study. Therefore, a phase II study (BREAK-MB) was initiated. Methods: Stage IV pts with ≥ 1 intracranial met (0.5 cm–4 cm assessed by MRI) without prior brain therapy (Cohort A) or with progression following prior brain therapy (Cohort B) were eligible with V600E/K mutation. Pts received dabrafenib 150 mg BID. The primary endpoint was investigator-assessed OIRR among V600E mutation-positive pts. Results: Overall, 172 pts were recruited. At interim analysis, of 127 pts enrolled (safety population), 41 (Cohort A n=24; Cohort B n=17) had reached 8-week disease assessment. Unconfirmed OIRR in Cohort A was 10/19, (53%; 95% CI: 28.9–75.6%) for V600E and 1/5 (20%; 95% CI: 0.5–71.6%) for V600K pts. In Cohort B unconfirmed OIRR was 8/15 (53%; 95% CI: 26.6%–78.7%) for V600E and 1/2 (50%; 95% CI: 1.3–98.7%) for V600K pts. Unconfirmed overall response rate (ORR) in Cohort A was 10/19 (53%; 95% CI: 28.9–75.6%) for V600E and 1/5 (20%; 95% CI: 0.5–71.6%) for V600K pts. In Cohort B unconfirmed ORR was 6/15 (40%; 95% CI: 16.3–67.7%) for V600E and 1/2 (50%; 95% CI: 1.3–98.7%) for V600K pts. In the safety population, 12/63 pts (19%) in Cohort A reported an SAE; 1 (2%) was fatal (cerebral hemorrhage). In Cohort B 15/64 pts (25%) reported an SAE; 1 (2%) was fatal (seizure). In Cohort A, 47 pts (75%) experienced AEs: 9 grade 3 (14%) and 3 grade 4 (5%). The most common AEs were headache (21%), hyperkeratosis and rash (17% each). In Cohort B, 47 pts (73%) experienced AEs: 12 grade 3 (19%) and 3 grade 4 (5%). The most common AEs were fatigue or nausea (22% each) and pyrexia (17%). Conclusions: Dabrafenib shows high clinical activity both in pts with intra- and extracranial mets with acceptable toxicity. Final data will be presented.",

author = "Kirkwood, {John M.} and Long, {Georgina V.} and Uwe Trefzer and Davies, {Michael A.} and Ascierto, {Paolo Antonio} and Chapman, {Paul B.} and Igor Puzanov and Axel Hauschild and Caroline Robert and Richard Kefford and Goodman, {Vicki L.} and Switzky, {Julie C.} and Swann, {R. Suzanne} and Anne-Marie Martin and Guckert, {Mary E.} and Streit, {Michael R. W.} and Dirk Schadendorf",

year = "2012",

month = may,

day = "20",

doi = "10.1200/jco.2012.30.15_suppl.8501",

language = "English",

volume = "30",

pages = "8501--8501",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

publisher = "American Society of Clinical Oncology",

number = "Supplement 15",

note = "48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) ; Conference date: 01-06-2012 Through 06-06-2012",

}

Kirkwood, JM, Long, GV, Trefzer, U, Davies, MA, Ascierto, PA, Chapman, PB, Puzanov, I, Hauschild, A, Robert, C, Kefford, R, Goodman, VL, Switzky, JC, Swann, RS, Martin, A-M, Guckert, ME, Streit, MRW & Schadendorf, D 2012, 'Break-MB: a phase II study assessing overall intracranial response rate (OIRR) to dabrafenib (GSK2118436) in patients (pts) with BRAF V600E/k mutation-positive melanoma with brain metastases (mets)', Journal of Clinical Oncology, vol. 30, no. Supplement 15, pp. 8501-8501. https://doi.org/10.1200/jco.2012.30.15_suppl.8501

Break-MB: a phase II study assessing overall intracranial response rate (OIRR) to dabrafenib (GSK2118436) in patients (pts) with BRAF V600E/k mutation-positive melanoma with brain metastases (mets). / Kirkwood, John M.; Long, Georgina V.; Trefzer, Uwe et al.
In: Journal of Clinical Oncology, Vol. 30, No. Supplement 15, 20.05.2012, p. 8501-8501.

Research output: Contribution to journal › Meeting abstract › peer-review

TY - JOUR

T1 - Break-MB

T2 - 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)

AU - Kirkwood, John M.

AU - Long, Georgina V.

AU - Trefzer, Uwe

AU - Davies, Michael A.

AU - Ascierto, Paolo Antonio

AU - Chapman, Paul B.

AU - Puzanov, Igor

AU - Hauschild, Axel

AU - Robert, Caroline

AU - Kefford, Richard

AU - Goodman, Vicki L.

AU - Switzky, Julie C.

AU - Swann, R. Suzanne

AU - Martin, Anne-Marie

AU - Guckert, Mary E.

AU - Streit, Michael R. W.

AU - Schadendorf, Dirk

PY - 2012/5/20

Y1 - 2012/5/20

N2 - Background: Melanoma brain mets carry a poor prognosis (median survival ≤4 months), for which more effective therapies are needed. Dabrafenib is a potent, selective oral inhibitor of mutated BRAF that has demonstrated clinical efficacy in pts with BRAF V600E/K mutant melanoma and previously untreated brain mets in a phase I study. Therefore, a phase II study (BREAK-MB) was initiated. Methods: Stage IV pts with ≥ 1 intracranial met (0.5 cm–4 cm assessed by MRI) without prior brain therapy (Cohort A) or with progression following prior brain therapy (Cohort B) were eligible with V600E/K mutation. Pts received dabrafenib 150 mg BID. The primary endpoint was investigator-assessed OIRR among V600E mutation-positive pts. Results: Overall, 172 pts were recruited. At interim analysis, of 127 pts enrolled (safety population), 41 (Cohort A n=24; Cohort B n=17) had reached 8-week disease assessment. Unconfirmed OIRR in Cohort A was 10/19, (53%; 95% CI: 28.9–75.6%) for V600E and 1/5 (20%; 95% CI: 0.5–71.6%) for V600K pts. In Cohort B unconfirmed OIRR was 8/15 (53%; 95% CI: 26.6%–78.7%) for V600E and 1/2 (50%; 95% CI: 1.3–98.7%) for V600K pts. Unconfirmed overall response rate (ORR) in Cohort A was 10/19 (53%; 95% CI: 28.9–75.6%) for V600E and 1/5 (20%; 95% CI: 0.5–71.6%) for V600K pts. In Cohort B unconfirmed ORR was 6/15 (40%; 95% CI: 16.3–67.7%) for V600E and 1/2 (50%; 95% CI: 1.3–98.7%) for V600K pts. In the safety population, 12/63 pts (19%) in Cohort A reported an SAE; 1 (2%) was fatal (cerebral hemorrhage). In Cohort B 15/64 pts (25%) reported an SAE; 1 (2%) was fatal (seizure). In Cohort A, 47 pts (75%) experienced AEs: 9 grade 3 (14%) and 3 grade 4 (5%). The most common AEs were headache (21%), hyperkeratosis and rash (17% each). In Cohort B, 47 pts (73%) experienced AEs: 12 grade 3 (19%) and 3 grade 4 (5%). The most common AEs were fatigue or nausea (22% each) and pyrexia (17%). Conclusions: Dabrafenib shows high clinical activity both in pts with intra- and extracranial mets with acceptable toxicity. Final data will be presented.

AB - Background: Melanoma brain mets carry a poor prognosis (median survival ≤4 months), for which more effective therapies are needed. Dabrafenib is a potent, selective oral inhibitor of mutated BRAF that has demonstrated clinical efficacy in pts with BRAF V600E/K mutant melanoma and previously untreated brain mets in a phase I study. Therefore, a phase II study (BREAK-MB) was initiated. Methods: Stage IV pts with ≥ 1 intracranial met (0.5 cm–4 cm assessed by MRI) without prior brain therapy (Cohort A) or with progression following prior brain therapy (Cohort B) were eligible with V600E/K mutation. Pts received dabrafenib 150 mg BID. The primary endpoint was investigator-assessed OIRR among V600E mutation-positive pts. Results: Overall, 172 pts were recruited. At interim analysis, of 127 pts enrolled (safety population), 41 (Cohort A n=24; Cohort B n=17) had reached 8-week disease assessment. Unconfirmed OIRR in Cohort A was 10/19, (53%; 95% CI: 28.9–75.6%) for V600E and 1/5 (20%; 95% CI: 0.5–71.6%) for V600K pts. In Cohort B unconfirmed OIRR was 8/15 (53%; 95% CI: 26.6%–78.7%) for V600E and 1/2 (50%; 95% CI: 1.3–98.7%) for V600K pts. Unconfirmed overall response rate (ORR) in Cohort A was 10/19 (53%; 95% CI: 28.9–75.6%) for V600E and 1/5 (20%; 95% CI: 0.5–71.6%) for V600K pts. In Cohort B unconfirmed ORR was 6/15 (40%; 95% CI: 16.3–67.7%) for V600E and 1/2 (50%; 95% CI: 1.3–98.7%) for V600K pts. In the safety population, 12/63 pts (19%) in Cohort A reported an SAE; 1 (2%) was fatal (cerebral hemorrhage). In Cohort B 15/64 pts (25%) reported an SAE; 1 (2%) was fatal (seizure). In Cohort A, 47 pts (75%) experienced AEs: 9 grade 3 (14%) and 3 grade 4 (5%). The most common AEs were headache (21%), hyperkeratosis and rash (17% each). In Cohort B, 47 pts (73%) experienced AEs: 12 grade 3 (19%) and 3 grade 4 (5%). The most common AEs were fatigue or nausea (22% each) and pyrexia (17%). Conclusions: Dabrafenib shows high clinical activity both in pts with intra- and extracranial mets with acceptable toxicity. Final data will be presented.

U2 - 10.1200/jco.2012.30.15_suppl.8501

DO - 10.1200/jco.2012.30.15_suppl.8501

M3 - Meeting abstract

SN - 0732-183X

VL - 30

SP - 8501

EP - 8501

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

IS - Supplement 15

Y2 - 1 June 2012 through 6 June 2012

ER -

Kirkwood JM, Long GV, Trefzer U, Davies MA, Ascierto PA, Chapman PB et al. Break-MB: a phase II study assessing overall intracranial response rate (OIRR) to dabrafenib (GSK2118436) in patients (pts) with BRAF V600E/k mutation-positive melanoma with brain metastases (mets). Journal of Clinical Oncology. 2012 May 20;30(Supplement 15):8501-8501. doi: 10.1200/jco.2012.30.15_suppl.8501

Break-MB: a phase II study assessing overall intracranial response rate (OIRR) to dabrafenib (GSK2118436) in patients (pts) with BRAF V600E/k mutation-positive melanoma with brain metastases (mets)

Abstract

Access to Document

Fingerprint

Cite this