Melanoma Brain Metastases

Oliva, Isabella Glitza; Tawbi, Hussein A.; Davies, Michael A.

doi:10.1097/ppo.0000000000000237

Cited by 46 publications

(27 citation statements)

References 37 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although current targeted and immune therapies have demonstrated activity in MBM, successful therapy is still a major challenge and an important area of current investigation (Glitza Oliva et al, 2017). MBM models are scarce and new therapies are needed urgently.…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Patient-Derived Xenograft Collection Representing the Heterogeneity of Melanoma

et al. 2017

Self Cite

View full text Add to dashboard Cite

Summary Therapy of advanced melanoma has been changing dramatically. Following mutational and biological sub-classification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX) and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological heterogeneity of melanoma. PDX have been characterized using targeted sequencing and protein arrays, and are clinically annotated. This exhaustive live tissue resource includes PDX from 57 samples resistant to targeted therapy, 61 samples from responders and non-responders to immune checkpoint blockade, and 31 samples from brain metastasis. Uveal, mucosal, and acral subtypes are represented as well. We show examples of pre-clinical trials that highlight how the PDX collection can be used to develop and optimize precision therapies, biomarkers of response, and the targeting of rare genetic subgroups.

show abstract

Section: Discussionmentioning

confidence: 99%

A Comprehensive Patient-Derived Xenograft Collection Representing the Heterogeneity of Melanoma

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Up to 60% of patients with metastatic melanoma develop brain metastasis. 108 OS for metastatic brain melanoma (MBM) is 4–6 months. 108 Despite the recent advances in management of metastatic melanoma with either immunotherapy or BRAFi (among those with BRAF V600 -mutated melanoma), MBM remains a therapeutic challenge and an area of unmet need.…”

Section: Braf Inhibitors In Management Of Metastatic Melanoma To Braimentioning

confidence: 99%

“… 108 OS for metastatic brain melanoma (MBM) is 4–6 months. 108 Despite the recent advances in management of metastatic melanoma with either immunotherapy or BRAFi (among those with BRAF V600 -mutated melanoma), MBM remains a therapeutic challenge and an area of unmet need. From the 6,000 patients who were enrolled in the pivotal studies that led to the approval of targeted or immunotherapy in metastatic melanoma, none included patients with previously untreated MBM.…”

Section: Braf Inhibitors In Management Of Metastatic Melanoma To Braimentioning

confidence: 99%

“…From the 6,000 patients who were enrolled in the pivotal studies that led to the approval of targeted or immunotherapy in metastatic melanoma, none included patients with previously untreated MBM. 87 , 88 , 108 …”

Section: Braf Inhibitors In Management Of Metastatic Melanoma To Braimentioning

confidence: 99%

“…Prior use of cytotoxic chemotherapy or temozolomide, a second-generation oral alkylating agent, showed poor activity against MBM with intracranial response of <10%. 108 , 109 A fotemustine Phase III randomized study that included 43 patients with MBM showed a brain response rate of only 5.9% compared with no response in the dacarbazine arm. 110 There are a growing number of trials that have shown activity of BRAFi therapy in patients with MBM ( Table 4 ).…”

Section: Braf Inhibitors In Management Of Metastatic Melanoma To Braimentioning

confidence: 99%

See 2 more Smart Citations

Mechanisms of resistance to BRAF and MEK inhibitors and clinical update of US Food and Drug Administration-approved targeted therapy in advanced melanoma

Kakadia

Yarlagadda

Awad

et al. 2018

OTT

208

201

View full text Add to dashboard Cite

Approximately 50% of melanomas harbor an activating BRAF mutation. Combined BRAF and MEK inhibitors such as dabrafenib and trametinib, vemurafenib and cobimetinib, and encorafenib and binimetinib are US Food and Drug Administration (FDA)-approved to treat patients with BRAFV600-mutated advanced melanoma. Both genetic and epigenetic alterations play a major role in resistance to BRAF inhibitors by reactivation of the MAPK and/or the PI3K–Akt pathways. The role of BRAF inhibitors in modulating the immunomicroenvironment and perhaps enhancing the efficacy of checkpoint inhibitors is gaining interest. This article provides a comprehensive review of mechanisms of resistance to BRAF and MEK inhibitors in melanoma and summarizes landmark trials that led to the FDA approval of BRAF and MEK inhibitors in metastatic melanoma.

show abstract

Melanoma brain metastasis presentation, treatment, and outcomes in the age of targeted and immunotherapies

Bander

Yuan

Carnevale

et al. 2021

Cancer

View full text Add to dashboard Cite

BACKGROUND: Historically, the prognosis for patients who have melanoma brain metastasis (MBM) has been dismal. However, breakthroughs in targeted and immunotherapies have improved long-term survival in those with advanced melanoma. Therefore, MBM presentation, prognosis, and the use of multimodality central nervous system (CNS)-directed treatment were reassessed. METHODS: In this retrospective study, the authors evaluated patients with MBM who received treatment at Memorial Sloan Kettering Cancer Center between 2010 and 2019. Kaplan-Meier methodology was used to describe overall survival (OS). Recursive partitioning analysis and timedependent multivariable Cox modeling were used to assess prognostic variables and to associate CNS-directed treatments with OS. RESULTS: Four hundred twenty-five patients with 2488 brain metastases were included. The median OS after an MBM diagnosis was 8.9 months (95% CI, 7.9-11.3 months). Patients who were diagnosed with MBM between 2015 and 2019 experienced longer OS compared to those who were diagnosed between 2010 and 2014 (OS, 13.0 months [95% CI, 10.47-17.06 months] vs 7.0 months [95% CI, 6.1-8.3 months]; P = .0003). Prognostic multivariable modeling significantly associated shortened OS independently with leptomeningeal dissemination (P < .0001), increasing numbers of brain metastases at diagnosis (P < .0001), earlier MBM diagnosis year (P = .0008), higher serum levels of lactate dehydrogenase (P < .0001), receipt of immunotherapy before MBM diagnosis (P = .003), and the presence of extracranial disease (P = .02). The use of different CNS-directed treatment modalities was associated with presenting symptoms, diagnosis year, number and size of brain metastases, and the presence of extracranial disease. Multivariable analysis demonstrated improved survival for patients who underwent craniotomy (P = .01). CONCLUSIONS: The prognosis for patients with MBM has improved within the last 5 years, coinciding with the approval of PD-1 immune checkpoint blockade and combined BRAF/MEK targeting. Improving survival reflects and may influence the willingness to use aggressive multimodality treatment for MBM.

show abstract

Melanoma Brain Metastases

Cited by 46 publications

References 37 publications

A Comprehensive Patient-Derived Xenograft Collection Representing the Heterogeneity of Melanoma

A Comprehensive Patient-Derived Xenograft Collection Representing the Heterogeneity of Melanoma

Mechanisms of resistance to BRAF and MEK inhibitors and clinical update of US Food and Drug Administration-approved targeted therapy in advanced melanoma

Melanoma brain metastasis presentation, treatment, and outcomes in the age of targeted and immunotherapies

Contact Info

Product

Resources

About