Dramatic clinical response following dabrafenib and trametinib therapy in a heavily pretreated low grade serous ovarian carcinoma patient with a BRAF V600E mutation

Mendivil, Alberto A.; Tung, Paul; Bohart, Randy; Bechtol, Karen A.; Goldstein, Bram H.

doi:10.1016/j.gore.2018.09.002

Cited by 18 publications

(12 citation statements)

References 20 publications

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“…Although, as encountered here, the mutations BRAF gene, lead to constitutive BRAF kinase phosphorylation of MEK and ERK kinases and sustained MAPK pathway signaling. Therefore, targeted therapy with BRAF inhibitors can be an effective alternative treatment for these patients (11,12,13). In summary, we described the rst case of perironeal serous borderline tumor with POLE E mutation and ultramutated pro le.…”

Section: Discussionmentioning

confidence: 87%

Peritoneal Serous Borderline Tumour with Ultra-Mutated NGS Profile Including POLE E, BRAF, RB1, HER2 and P53 Mutations : A Case Report.

Noël

Buonomo

Bouri

et al. 2020

Preprint

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Background: Serous borderline tumors of the peritoneum are rare low-grade epithelial proliferation with a tubal-type differentiation occurring in the pelvis or abdomen without underlying tissue invasion that resemble to ovarian serous borderline tumors but by definition without ovrian or tubal involvement. To date, the mutation status in molecular biology of these tumours remains largely unknown.Case presentation: Here we describe the case of a borderline peritoneal serous tumour which occurred in a 48 year old patient in whom an analysis of the mutation status by NGS technique identified a ultra-mutated profile including POLE E, BRAF, RB1, HER2 and p53 mutations.Conclusions: To the best of our knowledge, this particular mutation status has never been described in this type of tumour. It could represent an early event with transient mutations, most of them will not fixate on the genome.

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Section: Discussionmentioning

confidence: 87%

Peritoneal Serous Borderline Tumour with Ultra-Mutated NGS Profile Including POLE E, BRAF, RB1, HER2 and P53 Mutations : A Case Report.

Noël

Buonomo

Bouri

et al. 2020

Preprint

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“…In comparison, in malignant melanoma patients the median PFS is 11–15 months, and complete response is observed in 8–13% of the cases ( 14 , 18 ). There are a few recent reports on BRAF and MEK inhibitor combination therapy in patients with LGSOC ( 6 , 11 ). However, to our knowledge, there is no previously described case where complete response has been achieved in LGSOC with this treatment and no prior report on a patient benefiting for years.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, long-term survival has been reported in a patient with LGSOC treated with the BRAF inhibitor vemurafenib (10). In addition, there are a few recent reports on BRAF and MEK inhibitor combination therapy in patients with LGSOC (6,11).…”

Section: Introductionmentioning

confidence: 99%

Complete response with combined BRAF and MEK inhibition in BRAF mutated advanced low-grade serous ovarian carcinoma

Tholander

Koliadi

Botling

et al. 2020

Upsala Journal of Medical Sciences

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More effective treatments are needed for low-grade serous ovarian carcinoma (LGSOC). Our patient, who suffers from metastatic LGSOC, had received all established treatments. Sequencing analysis revealed an activating BRAF mutation. Therefore, combined treatment with BRAF and MEK inhibitors, which is the gold standard in malignant melanoma, was initiated. After eight months of therapy, the response was assessed as complete and the treatment is still, 3.5 years after initiation, of benefit. To our knowledge, no complete response on combined BRAF and MEK inhibitor treatment of low-grade serous ovarian cancer has previously been reported.

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“…65 Moreover, the use of selective inhibitors of the mitogen-activated protein kinase (MAPK) signaling pathway as BRAF and MEK inhibitors has been associated with promising results in some patients. 66 Further prospective studies are warranted to determine the optimal use of hormonal and targeted therapies for recurrent…”

Section: Treatmentmentioning

confidence: 99%

Low-grade epithelial ovarian cancer: what a radiologist should know

Elsherif

Javadi

Viswanathan

et al. 2019

BJR

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Ovarian cancer is responsible for the death of over 100,000 females annually. 1 Much of the published medical literature regards the various histologically distinct subtypes of epithelial ovarian neoplasms as one group, and almost all patients with advanced stage disease are treated with the standard therapy of debulking surgery followed by platinum-based adjuvant chemotherapy. However, recent studies have questioned this "one-size-fits-all" concept and advocated for another theory that ovarian cancer comprise of a spectrum of diverse tumors, each with characteristic histological and molecular features that determine its behavior and prognosis. 1-3 In 2004, Malpica and colleagues at the MD Anderson Cancer Center (MDACC) proposed a novel binary grading system for serous ovarian carcinoma, the most common histological subtype of ovarian cancer. This MDACC binary grading system was mainly based on nuclear atypia, in addition to the mitotic index. They found substantial correlation between tumor grade and survival rate. Bodurka et al 2 assessed the two-tier grading system in 290 patients with Stage III serous ovarian carcinoma and found that this grading system had minimal interobserver variability as it was reproducible among pathologists. Their study supported the theory that grade II and III tumors were better grouped together as they have a similar clinical outcome and prognosis. 2 Low-grade serous ovarian carcinomas are a distinct group with a longer progression-free survival (PFS) and overall survival (OS) compared to highgrade serous ovarian carcinomas (45 vs 19.8 and 126.2 vs 53.8, respectively). 2 Since the binary grading system helps to stratify the clinical outcomes and treatment strategies of ovarian neoplasms, the two-tier MDACC grading system is currently used for grading of serous ovarian carcinoma rather than the traditional three-tier grading system. 2,4,5 This article reviews the recent literature addressing the staging and follow-up of low-grade epithelial ovarian cancer with the main emphasis on serous ovarian cancer. clASSificAtion Embryologically, ovarian tumors are grouped into three major categories based on their origin: epithelial-stromal tumors, sex cord-stromal tumors, and germ cell tumors. Malignant epithelial tumors account for 90-98% of ovarian cancer and can be subdivided into five main groups: high-grade serous ovarian carcinoma (HGSOC) (70%), low-grade serous ovarian carcinoma (LGSOC) (<5%), clear cell carcinoma (10%), endometrioid carcinoma (EC) (10%) and mucinous carcinoma (1.5-3%). 6,7 Other less common subtypes of malignant epithelial neoplasms that are included in the new 2014 WHO Classification of Ovarian Cancer 8 include malignant Brenner tumors and seromucinous carcinoma. 9

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Dramatic clinical response following dabrafenib and trametinib therapy in a heavily pretreated low grade serous ovarian carcinoma patient with a BRAF V600E mutation

Cited by 18 publications

References 20 publications

Peritoneal Serous Borderline Tumour with Ultra-Mutated NGS Profile Including POLE E, BRAF, RB1, HER2 and P53 Mutations : A Case Report.

Peritoneal Serous Borderline Tumour with Ultra-Mutated NGS Profile Including POLE E, BRAF, RB1, HER2 and P53 Mutations : A Case Report.

Complete response with combined BRAF and MEK inhibition in BRAF mutated advanced low-grade serous ovarian carcinoma

Low-grade epithelial ovarian cancer: what a radiologist should know

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