Response rate to vemurafenib in patients with B-RAF-positive melanoma brain metastases

Dzienis, Marcin; Atkinson, Victoria

doi:10.1097/cmr.0000000000000068

Cited by 36 publications

(22 citation statements)

References 6 publications

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“…The physiochemical properties of vemurafenib including its hydrophilic and hydroscopic nature also would suggest its limited distribution in the brain [18,19]. However, vemurafenib has shown some activity in established brain metastases in some case reports and observational studies [7][8][9][10]. In addition, our retrospective review of patients who developed brain metastases during the study period showed that vemurafenib decreased the incidence of brain lesions in patients treated with the drug before the development of brain lesions.…”

Section: Discussionmentioning

confidence: 88%

“…However, patients with brain metastases were excluded from the pivotal vemurafenib study [6]. As a result, information on the impact of BRAF inhibitors on brain metastases is based mostly on single case reports or small case series [7][8][9][10]. In addition, the effect of BRAF on the risk of developing brain metastases is not well known [11].…”

Section: Introductionmentioning

confidence: 99%

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Impact of BRAF mutation and BRAF inhibition on melanoma brain metastases

et al. 2015

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The impact of BRAF mutations in metastatic melanoma on the incidence of brain metastases and melanoma prognosis and the effect of BRAF inhibitors on the incidence of brain metastases has not been defined. Therefore, a retrospective analysis of patients with metastatic melanoma treated at three institutions was carried out to examine the impact of BRAF mutations and a BRAF inhibitor, vemurafenib, on the incidence of brain metastases. A retrospective review of 436 records revealed no difference in the incidence of brain metastases between patients with BRAF-mutated tumors versus those without (incidence rate ratio=1.11, 95% confidence interval: 0.80-1.53; P=0.53). A lower incidence of brain metastases was observed in patients with BRAF-mutated tumors who took vemurafenib before the development of brain metastases versus those who did not (incidence rate ratio=0.51, 95% confidence interval: 0.30-0.86; P=0.009). Although treatment with vemurafenib led to improvement in extracranial disease control, it did not significantly affect progression of existing intracranial disease and survival in these patients (P=0.7). Although our previous preclinical data have indicated that penetration of vemurafenib into the brain is limited, our retrospective analysis showed that there was a lower incidence of brain metastases in patients with BRAF-mutated tumors who took vemurafenib before the diagnosis of brain metastases.

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Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Impact of BRAF mutation and BRAF inhibition on melanoma brain metastases

et al. 2015

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“…While data of the first studies did not allow drawing conclusions on vemurafenib intra-cerebral efficacy, various studies have shown in patients with V600E mutation an intracranial response rate of 16-50 %, with a progression-free survival of 3.9-4.6 months and an overall survival of 5-8 months, increased up to 13.7 months in a series of 12 patients in association with radiotherapy. The 6-month local control rate was of 75 % in this series [7,25,[28][29][30]. Patients with V600K mutation seem to be less responsive with an estimated progression-free survival of 2-4 months and overall survival of 4-5 months.…”

Section: Discussionmentioning

confidence: 94%

Incidence and characteristics of melanoma brain metastases developing during treatment with vemurafenib

et al. 2014

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Vemurafenib is indicated for the treatment of patients with BRAF (V600)-mutant metastatic melanoma. We studied for the first time the characteristics of brain metastases developed during treatment with vemurafenib in real-life conditions. We included all patients treated over 3 years with vemurafenib in our department for metastatic melanoma without initial brain involvement. Our primary endpoint was to assess the incidence of brain metastases in these patients. Our secondary endpoints were to identify the risk factors for metastases occurrence and their characteristics and course. In our retrospective cohort of 86 patients, 20% had developed brain metastases on average 5.3 months after vemurafenib initiation. The median follow-up was 9 months (1-26 months). Radiological examinations revealed multiple brain metastases in 41% of patients. The only risk factor for metastasis occurrence identified was a high number of metastatic sites when initiating vemurafenib (p = 0.045). Metastasis development was associated with a trend toward a decrease in overall survival from 12.8 to 8.5 months (p = 0.07) and a significant decrease in progression-free survival from 7 to 5 months (p = 0.04). Among the patients who developed brain metastases, 82% died, of whom 64% within 3 months, versus 58% of patients without brain metastases over the same period. The extra-cerebral disease was well controlled in 59% of patients during brain progression. In vemurafenib-treated melanoma patients, brain metastases are frequent and associated with a particularly poor prognosis. Because of their high frequency in patients with controlled extra-cerebral disease, brain explorations should be systematically performed during treatment.

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“…Dans une autre cohorte, l'effet du vémurafénib était analysé chez 22 patients avec mélanome BRAF muté et métastases céré-brales asymptomatiques [34]. Dans la cohorte A, les 12 patients n'ont pas reç u de traitement local préalablement, quatre patients atteints d'une maladie cérébrale progressive après traitement local ont été également inclus dans cette cohorte.…”

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