Phase II Trial (BREAK-2) of the BRAF Inhibitor Dabrafenib (GSK2118436) in Patients With Metastatic Melanoma

Ascierto, Paolo A.; Minor, David R.; Ribas, Antoni; Lebbe, Célèste; O’Hagan, Anne; Arya, Niki; Guckert, Mary; Schadendorf, Dirk; Kefford, Richard; Grob, Jean-Jacques; Hamid, Omid; Amaravadi, Ravi K.; Simeone, Ester; Wilhelm, Tabea; Kim, Kevin B.; Long, Georgina V.; Martin, Anne Marie; Mazumdar, Jolly; Goodman, Vicki; Trefzer, Uwe

doi:10.1200/jco.2013.49.8691

Cited by 387 publications

(277 citation statements)

References 20 publications

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“…The BREAK-3 study also provided further evidence in support of the finding from the BREAK-2 Phase II study of dabrafenib that the presence of circulating free DNA harboring the BRAF V600E mutation (cfDNA BRAF V600E ) is related to a worse overall response rate (ORR) and progression-free survival (PFS) [5]. In the Break-3 study, 44% of patients still on treatment with dabrafenib without progression had no detectable levels of cfDNA BRAF V600E [2].…”

Section: Brafisupporting

confidence: 60%

Combination Approaches and Anti-PD1 Therapies: the Focus of New Research at ESMO and SMR

Ascierto¹

2015

Melanoma Manag.

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Research into the treatment of melanoma is continuing to progress, and both the European Society of Medical Oncology (26–30 September, Madrid, Spain) and the Society of Melanoma Research (13–16 November, Zurich, Switzerland) 2014 annual meetings provided important updates in this field. Areas of particular focus included combinations of a BRAF inhibitor with a MEK inhibitor (COMBI-v and CoBRIM trials) and new data on anti-PD1 therapies (nivolumab and pembrolizumab). Overall, the data reported at these two meetings again suggest that melanoma is perhaps the most dynamic field of oncology, with continuing advances in management of the disease that may improve outcomes for patients in clinical practice.

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Section: Brafisupporting

confidence: 60%

Combination Approaches and Anti-PD1 Therapies: the Focus of New Research at ESMO and SMR

Ascierto¹

2015

Melanoma Manag.

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“…In addition, the median progression-free survival of 8.8 months in the dabrafenib-only group was longer than that in previous trials of dabrafenib and vemurafenib in which the median progression-free survival was 5.5 to 6.9 months. [1][2][3][4]17,[27][28][29] The long plateau at the median progression-free survival point in the dabrafenib-only group may account in part for its increased value in our study (Fig. 1A).…”

Section: Discussionmentioning

confidence: 73%

Combined BRAF and MEK Inhibition versus BRAF Inhibition Alone in Melanoma

Long¹,

Stroyakovskiy²,

Gogas³

et al. 2014

N Engl J Med

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“…12,13,32 The results of this study suggest that patients with V600K/R melanoma have a lower response rate and shorter PFS than patients with V600E melanoma but similar OS. The mechanisms behind this are not clear, but the differences in age, chronic sun damage, and mutational load in V600E and V600K/R melanoma suggest biologically distinct subtypes that may warrant different treatments.…”

Section: Discussionmentioning

confidence: 82%

Clinicopathologic features associated with efficacy and long‐term survival in metastatic melanoma patients treated with BRAF or combined BRAF and MEK inhibitors

Menzies

Wilmott

Drummond

et al. 2015

Cancer

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BACKGROUND:The degree of response and the duration of survival of patients treated with mitogen-activated protein kinase (MAPK) inhibitors are highly variable. Whether baseline clinicopathologic factors can predict the clinical course with treatment is largely unknown. METHODS: For 142 consecutive immunotherapy-and MAPK inhibitor-naive patients with BRAF-mutant metastatic melanoma who were treated during clinical trials with BRAF inhibitors (n 5 111) or a combination of dabrafenib and trametinib (n 5 31), clinicopathologic factors were correlated with the response to MAPK inhibitors and survival. RESULTS: The median follow-up was 15.7 months (range, 0.6-60.5 months). The 2-, 3-, and 4-year overall survival (OS) rates were 43%, 24%, and 24%, respectively. A multivariate analysis demonstrated that the only clinicopathologic factors associated with longer progression-free survival (PFS) and OS were female sex and a normal pretreatment serum lactate dehydrogenase (LDH) level. The BRAF V600E genotype and an absence of primary melanoma ulceration were also independently associated with longer PFS but not OS. The median OS was 23.5 months for patients with normal LDH levels and 7.3 months for those with elevated LDH levels (hazard ratio, 0.31; P < .001). Complete responders had the best survival, but disease progression still occurred in 2 of 7 patients. CONCLUSIONS: Long-term survival occurs for a minority of patients receiving MAPK inhibitor treatment alone. Sex, serum LDH, BRAF genotype, and primary melanoma ulceration status are independent factors associated with treatment outcomes. Patients with a complete response to treatment have the best survival, but relapses still occur. Cancer 2015;121:3826-35.

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Phase II Trial (BREAK-2) of the BRAF Inhibitor Dabrafenib (GSK2118436) in Patients With Metastatic Melanoma

Abstract: Dabrafenib was well tolerated and clinically active in patients with BRAF(V600E/K) mut(+) MM. cfDNA may be a useful prognostic and response marker in future studies.

Cited by 387 publications

References 20 publications

Combination Approaches and Anti-PD1 Therapies: the Focus of New Research at ESMO and SMR

Combination Approaches and Anti-PD1 Therapies: the Focus of New Research at ESMO and SMR

Combined BRAF and MEK Inhibition versus BRAF Inhibition Alone in Melanoma

Clinicopathologic features associated with efficacy and long‐term survival in metastatic melanoma patients treated with BRAF or combined BRAF and MEK inhibitors

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