Cutaneous toxicities associated with vemurafenib therapy in 107 patients with<i>BRAF</i>V600E mutation-positive metastatic melanoma, including recognition and management of rare presentations

Sinha, R. K.; Larkin, James; Gore, Martin; Fearfield, L.

doi:10.1111/bjd.13958

Cited by 37 publications

(50 citation statements)

References 26 publications

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“…b). High‐grade rash was reported in five trials and occurred in 396 out of 4001 total events; overall prevalence of high‐grade rash was 12.00% (95% CI 0.03–0.38) and Q = 495 ( P < 0.01; I 2 = 99%) (Fig. b).…”

Section: Resultsmentioning

confidence: 98%

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Systematic review and meta-analysis of prevalence of dermatological toxicities associated with vemurafenib treatment in patients with melanoma

Chen

Zhou

2018

Clin Exp Dermatol

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Summary Background Vemurafenib has been linked to dermatological adverse events in patients with melanoma, including an increased risk of rash, cutaneous squamous cell carcinoma, photosensitivity reaction and keratoacanthoma. However, there has been no systematic attempt to assess the dermatological toxicity data of vemurafenib associated with melanoma treatment. Aim To evaluate the point prevalence of dermatological toxicities associated with vemurafenib treatment in patients with melanoma. Methods Searches were conducted of the electronic databases PubMed and EMBASE and of conference abstracts published by the American Society of Clinical Oncology. Eligible studies included prospective clinical trials and expanded‐access programmes (i.e. outside a clinical trial) of patients with melanoma assigned to vemurafenib treatment. Outcomes included prevalence of dermatological toxicities treated with vemurafenib. Statistical analyses were performed using the R2.8.1 meta package. Results In total, 11 studies comprising 4197 patients were included in the meta‐analysis. For patients assigned to vemurafenib, the overall prevalence of all‐grade cutaneous squamous cell carcinoma (cSCC) was 18.00% (95% CI 12.00–26.00%), rash 45.00% (95% CI 34.00–57.00%), photosensitivity reaction (PR) 30.00% (95% CI 23.00–38.00%), keratoacanthoma (KA) 10.00% (95% CI 6.00–15.00%) and hand–foot skin reaction (HFSR) 9.00% (95% CI 4.00–20.00%), while the prevalence of high‐grade events was: cSCC 16.00% (95% CI 11.00–23.00%), rash 12.00% (95% CI 3.00–38.00%), PR 4% (95% CI 2.00–8.00%) and KA 6.00% (95% CI 5.00–7.00%). Conclusion The most frequent dermatological toxicities associated with vemurafenib treatment in patients with melanoma were cSCC, rash, PR and KA. These data may be useful for estimation of the efficacy and safety of the drug during clinical treatment and for reducing the prevalence of adverse reactions to vemurafenib treatment in patients with melanoma.

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Section: Resultsmentioning

confidence: 98%

“…Analysis of the prevalence of all‐grade cSCC associated with heterogeneity in patients with melanoma was performed for eight studies . Testing for interstudy heterogeneity gave significant results [ Q = 85.56; P < 0.01; I 2 = 91.8% (high heterogeneity was I 2 > 50%)].…”

Section: Resultsmentioning

confidence: 99%

Systematic review and meta-analysis of prevalence of dermatological toxicities associated with vemurafenib treatment in patients with melanoma

Chen

Zhou

2018

Clin Exp Dermatol

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“…3 According to a previous report, folliculitis was observed in 6-9% of patients who received vemurafenib, 4 while we postulate that the actual diagnosis may be acneiform eruption in some of these cases. In addition, BRAFi is known to induce other cutaneous adverse events related with keratinocyte proliferation, such as keratosis pilaris-like eruption, keratoacanthoma and squamous cell carcinoma.…”

mentioning

confidence: 73%

“…In addition, BRAFi is known to induce other cutaneous adverse events related with keratinocyte proliferation, such as keratosis pilaris-like eruption, keratoacanthoma and squamous cell carcinoma. 4 Recent studies have shown that paradoxical activation of mitogen-activated protein kinase (MAPK) pathway via CRAF, which is another component of RAF kinases, leads to increased keratinocyte proliferation. 5 Therefore, we hypothesize that BRAFi may induce the formation and increase of comedones especially in patients with the history of acne, who already have numerous comedones and microcomedones in their skin, through follicular keratinocyte proliferation by activation of the MAPK pathway.…”

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confidence: 99%

Case of severe acneiform eruptions associated with the BRAF inhibitor vemurafenib

Ansai

Fujikawa

Shimomura

et al. 2016

The Journal of Dermatology

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“…The treatment of patients with melanoma with the BRAF inhibitors vemurafenib or dabrafenib is associated with a multitude of cutaneous toxicities like UVA-dependent photosensitivity, follicular hyperkeratosis, papulopustular exanthema, erythema nodosum, palmoplantar hyperkeratosis, cysts, miliae and keratoacanthoma [4,13,[29][30][31][32][33][34][35][36]. Other side effects are neoplastic by nature, such as squamous cell and basal cell carcinoma or additional primary melanomas.…”

Section: Adverse Side Effects Of Braf Inhibitor Therapymentioning

confidence: 99%

Radiotherapy with BRAF Inhibitor Therapy for Melanoma: Progress and Possibilities

et al. 2015

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The introduction of small molecule BRAF(V600) kinase inhibitors represents a milestone in the targeted therapy of patients with metastatic melanoma by a significant increase in therapeutic efficacy in terms of overall and progression-free survival compared with conventional chemotherapy. Beside BRAF(V600) inhibitor treatment, radiotherapy is a further mainstay for the therapy of metastatic melanoma and thus a concomitant or sequential application of BRAF(V600) inhibitors and radiotherapy is inevitable. Recent reports show a significant radiosensitization of the irradiated healthy tissue in patients with melanoma after the combination of radiotherapy and BRAF(V600) inhibitors, evoking concern in clinical practice. We review interactions of BRAF(V600) inhibitors and radiation with regard to antitumor effects and an increased radiotoxicity in the healthy tissue.

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Cutaneous toxicities associated with vemurafenib therapy in 107 patients withBRAFV600E mutation-positive metastatic melanoma, including recognition and management of rare presentations

Abstract: Vemurafenib appears to have a predictable and manageable AE profile. Proactive management can limit the impact of AEs on patients, allowing treatment to continue despite toxicities.

Cited by 37 publications

References 26 publications

Systematic review and meta-analysis of prevalence of dermatological toxicities associated with vemurafenib treatment in patients with melanoma

Systematic review and meta-analysis of prevalence of dermatological toxicities associated with vemurafenib treatment in patients with melanoma

Case of severe acneiform eruptions associated with the BRAF inhibitor vemurafenib

Radiotherapy with BRAF Inhibitor Therapy for Melanoma: Progress and Possibilities

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