Current Controversies and Challenges on BRAF V600K-Mutant Cutaneous Melanoma

Nepote, Alessandro; Avallone, Gianluca; Ribero, Simone; Cavallo, Francesco; Roccuzzo, Gabriele; Mastorino, Luca; Conforti, Claudio; Paruzzo, Luca; Poletto, Stefano; Schianca, Fabrizio Carnevale; Quaglino, Pietro

doi:10.3390/jcm11030828

Cited by 18 publications

(11 citation statements)

References 40 publications

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“…However, in our study, all patients with BRAF mutant melanoma were treated with TTs as first-line therapy, so our results cannot support this hypothesis. 21 Our study demonstrated that patients treated with ICI or TT had longer survival than those treated with conventional chemotherapy or those not treated with systemic therapy. In addition, there was no difference between the effectiveness of single-agent ICI, COMBI-ICIs, and TT, regardless of BRAF V600 mutational status.…”

Section: Discussionmentioning

confidence: 51%

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A single‐center retrospective analysis of prognoses in patients with melanoma brain metastases and effectiveness of treatment in Japan

Wada,

Ogata,

Kashihara

et al. 2023

Cancer Medicine

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BackgroundMelanoma brain metastasis (MBM) has a poor prognosis, although recent treatments, including immune checkpoint inhibitors and targeted therapy, have improved the prognosis. However, these systemic therapies have been reported to be less efficient for Asian patients. We investigated the survival of Asian patients with MBM and the effectiveness of systemic therapies.MethodsWe retrospectively reviewed the survival rates of patients diagnosed with MBM between January 2011 and December 2021 at the National Cancer Center Hospital in Tokyo, Japan. In addition, we identified factors associated with survival using Cox regression analysis.ResultsA total of 135 patients were included. The median overall survival (OS) after an MBM diagnosis was 7.8 months (95% confidence interval [CI] 6.1–9.6). The 6‐month and 1‐year survival rates were 60.7% and 34.8%, respectively. We identified the prognostic factors of MBM, including non‐acral primary location, low serum LDH levels, systemic therapy of single‐agent immune checkpoint inhibitors (ICIs) or targeted therapies (TTs), and radiotherapy of stereotactic irradiation (STI). We found no significant difference in effectiveness between single‐agent ICIs, the combination of Nivolumab and Ipilimumab (COMBI‐ICI), and TTs (COMBI‐ICI vs. single‐agent ICI, hazard ratio 0.71, 95% confidence interval 0.27–1.88, p = 0.49; COMBI‐ICI vs. TT: hazard ratio 0.46, 95% confidence interval 0.14–1.55, p = 0.21).ConclusionsSystemic therapy and radiotherapy have improved the survival of MBM patients, but the survival of Asian patients remains poor. Our findings suggest that COMBI‐ICIs are not significantly more effective than single‐agent ICI or TT in treating MBM.

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Section: Discussionmentioning

confidence: 51%

“…It has been reported that patients with a V600K mutation may respond better to ICIs compared to those with a V600E mutation. However, in our study, all patients with BRAF mutant melanoma were treated with TTs as first‐line therapy, so our results cannot support this hypothesis 21 …”

Section: Discussionmentioning

confidence: 70%

A single‐center retrospective analysis of prognoses in patients with melanoma brain metastases and effectiveness of treatment in Japan

Wada,

Ogata,

Kashihara

et al. 2023

Cancer Medicine

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“…Furthermore, MMs harboring BRAF V600K mutation are considered as more aggressive than MMs with BRAF V600E mutation [ 41 ]. This characteristic suggests that the mutational spectrum of the BRAF gene should be fully described and that it may be considered as an essential criterion in MM diagnosis and therapeutic management [ 42 ]. No BRAF V600K mutation was detected in our study group, a finding consistent with a lower frequency of V600K mutations compared to V600E mutations reported in the literature [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

BRAF V600E Mutation in Malignant Melanoma—A Romanian Research Experience

Avădănei,

Căruntu,

Nucă

et al. 2024

Medicina

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Background and Objectives: The most common mutation in malignant melanoma (MM) is the single-point mutation of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) oncogene. Our study aims to evaluate BRAF V600E mutation, highlighting its frequency differences in primary versus metastatic MM. Materials and Methods: The study group comprised 133 patients diagnosed with MM in several county hospitals of the north-eastern region of Romania who have been assigned for investigation into BRAF V600E mutation in the private medical system. The material consisted of archived formalin-fixed paraffin-embedded (FFPE) blocks. BRAF V600E mutation was identified using the fully automated IdyllaTM BRAF mutation test system. Results: Out of the total of 133 cases, 78 cases were primary tumors, while 55 cases were metastatic MMs. Genetic analysis revealed the presence of BRAF V600E mutation in 66 cases (49.62%) and the wild-type genotype in 67 cases (50.37%). We found a statistically significant difference of the mutation frequency according to age (p = 0.0072). The mutated genotype was found in 45 cases out of 78 primary MMs (57.69%) and in 21 cases out of 55 secondary MMs (38.18%), with a statistically significant difference in favor of primary tumors (p = 0.0413). The correlations between the histopathological types, Clark’s level, Breslow index, ulceration, and lymphovascular invasion, respectively, and the mutated genotype were not statistically significant. BRAF V600E mutation was identified in 15 out of 40 secondary tumors with lymph node location (37.5%) and in 6 out of 15 secondary tumors with another location (40%) without statistically significant differences between the mutation frequency and the location of the secondary tumors. Conclusions: Our results support MM high genetic heterogeneity, pointing out the relationship between BRAF V600E mutation and several clinicopathological characteristics, in primary and metastatic MMs, stressing the importance of BRAF testing implementation in Romania.

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“…Although treatment with BRAF/MEK combinatory regimens such as dabrafenib + trametinib, vemurafenib + cobimetinib, and encorafenib + binimetinib, as well as with immunomodulators such as pembrolizumab and iplimumab, have shown some efficacy in V600K-mutant melanoma, evidence is not strong enough to make any formal first-line treatment recommendation for melanoma patients with the V600K mutation. Moving forward, the BRAF V600K driver mutation should be independently investigated in greater detail to formulate specified and evidence-backed recommendations of treatments for patients with this mutation, as their prognosis is currently still poor [ 69 ].…”

Section: Brafmentioning

confidence: 99%

Treatment of Metastatic Melanoma with a Combination of Immunotherapies and Molecularly Targeted Therapies

Rager

Eckburg

Patel

et al. 2022

Cancers

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Melanoma possesses invasive metastatic growth patterns and is one of the most aggressive types of skin cancer. In 2021, it is estimated that 7180 deaths were attributed to melanoma in the United States alone. Once melanoma metastasizes, traditional therapies are no longer effective. Instead, immunotherapies, such as ipilimumab, pembrolizumab, and nivolumab, are the treatment options for malignant melanoma. Several biomarkers involved in tumorigenesis have been identified as potential targets for molecularly targeted melanoma therapy, such as tyrosine kinase inhibitors (TKIs). Unfortunately, melanoma quickly acquires resistance to these molecularly targeted therapies. To bypass resistance, combination treatment with immunotherapies and single or multiple TKIs have been employed and have been shown to improve the prognosis of melanoma patients compared to monotherapy. This review discusses several combination therapies that target melanoma biomarkers, such as BRAF, MEK, RAS, c-KIT, VEGFR, c-MET and PI3K. Several of these regimens are already FDA-approved for treating metastatic melanoma, while others are still in clinical trials. Continued research into the causes of resistance and factors influencing the efficacy of these combination treatments, such as specific mutations in oncogenic proteins, may further improve the effectiveness of combination therapies, providing a better prognosis for melanoma patients.

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Current Controversies and Challenges on BRAF V600K-Mutant Cutaneous Melanoma

Cited by 18 publications

References 40 publications

A single‐center retrospective analysis of prognoses in patients with melanoma brain metastases and effectiveness of treatment in Japan

A single‐center retrospective analysis of prognoses in patients with melanoma brain metastases and effectiveness of treatment in Japan

BRAF V600E Mutation in Malignant Melanoma—A Romanian Research Experience

Treatment of Metastatic Melanoma with a Combination of Immunotherapies and Molecularly Targeted Therapies

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