Vemurafenib and Radiosensitization

Boussemart, Lise; Boivin, C.; Claveau, Joël; Tao, Yungan; Tomasic, Gorana; Routier, Émilie; Mateus, Christine; Deutsch, Éric; Robert, Caroline

doi:10.1001/jamadermatol.2013.4200

Cited by 81 publications

(60 citation statements)

References 11 publications

(7 reference statements)

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“…Because of the reported dermal reactions from radiation therapy and BRAF inhibitor therapy, BRAF inhibitors may cause radiosensitization. 2 It was noted that, in a melanoma cell line, the addition of targeted agents to inhibit BRAF can enhance radiosensitization. Radiation therapy has been shown to increase permeability in the blood-brain barrier.…”

Section: Discussionmentioning

confidence: 99%

“…40 In a case report by Anker et al, 1 a patient with melanoma who was treated with vemurafenib experienced in-field hepatic injury with fatal hepatic hemorrhage after palliative spine radiation. Others have reported varying skin, [1][2][3]13,31,36,41 lung, and bowel toxicities in patients after treatment with both radiation and BRAF inhibitors. The degree and length of the duration of these toxicities are concerning.…”

Section: Discussionmentioning

confidence: 99%

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Local control after stereotactic radiosurgery for brain metastases in patients with melanoma with and without BRAF mutation and treatment

Ly¹,

Bagshaw²,

Anker

et al. 2015

JNS

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OBJECT BRAF inhibitors improve progression-free and overall survival in patients with metastatic melanoma. Brain metastases are common, and stereotactic radiosurgery (SRS) has been used, resulting in excellent local control. Because BRAF inhibitors are associated with intracranial responses, the authors hypothesized that BRAF inhibitors would improve local control in patients with melanoma who are receiving SRS for brain metastases. METHODS The authors retrospectively identified patients with metastatic melanoma who had been tested for BRAF mutation and treated with SRS for brain metastases. Patients with previous resection, multiple brain metastases, or multiple courses of SRS were eligible. SRS was delivered in a single fraction to a median dose of 2000 cGy. Patients with a BRAF mutation were treated with a BRAF inhibitor on the basis of physician preference. RESULTS The authors identified 52 patients who were treated in 82 treatment sessions for 185 brain metastases and 13 tumor beds. At a median follow-up of 10.5 months, the 1-year local control rate was 69.2%. At 1 year, the local control rate for brain metastases in patients with BRAF mutation with BRAF treatment was 85.0%, and the local control rate for brain metastases in those without BRAF treatment was 51.5% (p = 0.0077). The rates of distant brain failure, freedom from whole-brain radiation, and overall survival were not different on the basis of BRAF mutation status or inhibitor therapy. The number of new intratumoral hemorrhages after SRS was increased significantly in patients with BRAF treatment. CONCLUSIONS Treatment with BRAF inhibitors was associated with improved local control after SRS in patients with melanoma and brain metastases. An increased number of intratumoral hemorrhages was associated with BRAF inhibitor therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Local control after stereotactic radiosurgery for brain metastases in patients with melanoma with and without BRAF mutation and treatment

Ly¹,

Bagshaw²,

Anker

et al. 2015

JNS

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“…This observation suggests that targeted therapies, particularly tyrosine kinase inhibitors, should be added to the list of radiation recall dermatitis-inducing substances. Also, for vemurafenib, the reports on a radiation-sensitizing and recall phenomenon are gradually increasing (table 1) [19,20,21,22,23,24,25]. The clinical presentations, however, are heterogeneous, applying sequential or combined approaches of vemurafenib and radiation.…”

Section: Discussionmentioning

confidence: 99%

Vemurafenib-Induced Radiation Recall Dermatitis: Case Report and Review of the Literature

Conen¹,

Mosna-Firlejczyk²,

Rochlitz³

et al. 2014

Dermatology

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The cutaneous effects of BRAF (serine/threonine protein kinase B-raf) inhibitors such as vemurafenib remain poorly defined. Rash, squamous cell carcinoma, keratoacanthoma and photosensitivity are the most common grade 2 or 3 adverse events observed in clinical trials. We here report the case of a patient with a BRAF V600E mutated metastatic melanoma who developed severe radiation recall dermatitis 6 weeks after completing radiotherapy. Vemurafenib treatment had been initiated 1 week before the development of dermatitis because of rapidly progressing disease. Upon topical treatment of the affected skin areas, clinical symptoms regressed over a period of 2 months, although vemurafenib was continuously administered. As our case goes in line with other reports, we believe that physicians should be aware of this additional cutaneous side effect of vemurafenib and that continuation of the treatment is safe when close clinical control and interdisciplinary management can be provided.

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“…Caution should be employed in combining concurrent BRAF inhibitor therapy and radiotherapy (especially to large treatment fields) due to apparent radiosensitization of normal tissues and an increased risk of AEs [Boussemart et al 2013;Merten et al 2014;Satzger et al 2013]. Forschner and colleagues reported on two patients that developed radiation recall pneumonitis [Forschner et al 2014].…”

Section: Toxicity Of Braf and Mek Inhibitionmentioning

confidence: 99%

Therapeutic approach to treating patients with BRAF-mutant lung cancer: latest evidence and clinical implications

Langen

Smit

2016

Ther Adv Med Oncol

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Lung adenocarcinoma is known for its high rate of somatic mutations and genomic rearrangements. The identification of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements that sensitize tumors to specific drugs has changed the therapeutic approach and prognosis in these molecularly-defined subgroups. Several other key genetic alterations have been identified, of which BRAF mutations are found in 4% of non-small cell lung cancer (NSCLC) cases. Targeted drugs against BRAF and downstream MEK were recently approved for the treatment of BRAF-positive melanoma and have entered clinical evaluation in NSCLC. In this review we discuss the latest evidence on the treatment of BRAF-mutated NSCLC, including tumor biology, targeted treatment with BRAF and MEK inhibitors, therapeutic resistance and strategies to overcome resistance.

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Vemurafenib and Radiosensitization

Cited by 81 publications

References 11 publications

Local control after stereotactic radiosurgery for brain metastases in patients with melanoma with and without BRAF mutation and treatment

Local control after stereotactic radiosurgery for brain metastases in patients with melanoma with and without BRAF mutation and treatment

Vemurafenib-Induced Radiation Recall Dermatitis: Case Report and Review of the Literature

Therapeutic approach to treating patients with BRAF-mutant lung cancer: latest evidence and clinical implications

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