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

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10.1200/jco.2012.30.15_suppl.8501

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

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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

Kirkwood, John M. ; Long, Georgina V. ; Trefzer, Uwe ; Davies, Michael A. ; Ascierto, Paolo Antonio ; Chapman, Paul B. ; Puzanov, Igor ; Hauschild, Axel ; Robert, Caroline ; Kefford, Richard ; Goodman, Vicki L. ; Switzky, Julie C. ; Swann, R. Suzanne ; Martin, Anne-Marie ; Guckert, Mary E. ; Streit, Michael R. W. ; Schadendorf, Dirk. / 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). In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. Supplement 15. pp. 8501-8501.

@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 = "1527-7755",

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

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

VL - 30

SP - 8501

EP - 8501

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 1527-7755

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. 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)

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