Treatment with combined dabrafenib and trametinib in BRAFV600E-mutated metastatic malignant melanoma: a case of long-term complete response after treatment cessation

Brugnara, S.; Sicher, Mariacristina; Bonandini, Elena; Donner, Davide; Chierichetti, Franca; Barbareschi, Mattia; Girardelli, Carlo Renè; Caffo, Orazio

doi:10.7573/dic.212515

Cited by 9 publications

(6 citation statements)

References 22 publications

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“…Brugnara et al presented a stage 4 melanoma which was treated with dabrafenib and trametinib combination achieved complete metabolic response. 14 After 31 months, the treatment was interrupted for the patient's decision and follow-up PET scans confirmed the metabolic response. Unlike their case that was treated with BRAF and MEK inhibitor combination therapy, our patient received only vemurafenib alone.…”

Section: Discussionmentioning

confidence: 99%

Treatment exceeds expectations with vemurafenib monotherapy in a patient with BRAF^V600E-mutant metastatic melanoma

Yılmaz

Mese

2020

J Oncol Pharm Pract

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Introduction Patients with distant metastatic melanoma has a poor prognosis, with a reported median survival time of six to eight months. In modern era, survival has prolonged with the immunotherapy and targeted therapy options. Potent and selective BRAF inhibitors have been developed that specifically inhibit mutated BRAF over other RAF kinases. Vemurafenib was the first selective tyrosine kinase inhibitor developed to target the V600E allele of BRAF-mutant melanoma. Case Report In this report, we present a case of BRAFV600E-mutant metastatic melanoma, which is being treated with vemurafenib monotherapy with complete response for about seven years. Management and Outcome The patient is still being treated with vemurafenib and radiologic complete response is ongoing for about seven years. Discussion Patients treated with BRAF inhibitors monotherapy had promising response rates and improvement in the progression-free survival and overall survival, but melanoma cells became resistant very quickly, affecting the progression. In this case, we present a case that has permanent response to vemurafenib monotherapy.

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Section: Discussionmentioning

confidence: 99%

Treatment exceeds expectations with vemurafenib monotherapy in a patient with BRAF^V600E-mutant metastatic melanoma

Yılmaz

Mese

2020

J Oncol Pharm Pract

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“…This latter frequency matches the expected overall response rate to the combination of BRAFi and MEKi in BRAF-mutated treatment-naïve patients, No correlative data between specific reasons of interruption (toxicity, complete response or other causes) and response was, however, provided. In small retrospective series of patients in complete response during BRAFi ± MEKi, treatment-related toxicity was the most reported cause of interruption (47)(48)(49). Approximately 50% of these patients experienced disease progression at various times from discontinuation and retreatment with BRAFi/MEKi, and no particular correlation between the occurrence of previous toxicity and outcome was reported.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Rechallenge With BRAF and MEK Inhibitors in Metastatic Melanoma: A Further Therapeutic Option in Salvage Setting?

et al. 2021

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BackgroundThe combination of BRAF and MEK inhibitors represents the standard of care treatment for patients with metastatic BRAF-mutated melanoma, notwithstanding the high frequency of emergent resistance. Moreover, therapeutic options outside clinical trials are scarce when patients have progressed after both targeted therapy and therapy with immune checkpoint inhibitors. In this article, we report our experience with targeted therapy rechallenging with BRAF and MEK inhibitors in patients with metastatic BRAF-mutated melanoma after progression with kinase inhibitors and immunotherapy.MethodsFour patients with metastatic BRAF-mutated melanoma were rechallenged with BRAF and MEK inhibitors after progression with targeted therapy and subsequent immunotherapy (checkpoint inhibitors).ResultsTwo patients (one of them was heavily pretreated) had partial response over 36 months (with local treatment on oligoprogression disease) and 10 months, respectively. A third patient with multisite visceral disease and high serum levels of lactate dehydrogenase had a short-lived clinical benefit rapidly followed by massive progression of disease (early progressor). The fourth patient, currently on treatment with BRAF/MEK inhibitors, is showing a clinical benefit and radiological stable disease over 3 months of therapy. Adverse events were manageable, similar to those reported during the first targeted therapy; the treatment was better tolerated at rechallenge compared with the first treatment by two out of four patients.

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“…In patients with CR, the 3-year PFS rate was 67, 40% at 5 years and the median PFS was 39.6 months ( 36 ). Furthermore, a case of long-term complete response 18 months after treatment discontinuation, has been reported ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

A Rare Case of Pituitary Melanoma Metastasis: A Dramatic and Prolonged Response to Dabrafenib-Trametinib Therapy

et al. 2020

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Introduction: Pituitary metastases (PM) are rare events and to date only very few cases of melanoma PM have been described in literature up to now. Case Presentation: We describe the clinical history of a 33-year-old male patient who underwent surgical excision of an inter-scapular melanoma in 2008. The subsequent follow-up was negative for ∼10 years. In September 2018, due to the onset of a severe headache, the patient underwent a brain magnetic resonance imaging, which showed an expansive mass in the saddle and suprasellar region with a maximum diameter of 17 mm. Pituitary function tests and visual field were normal. Worsening of the headache and the appearance of a left eye ptosis led the patient to surgical removal of the lesion in October 2018. The histological examination unexpectedly showed metastasis of the melanoma. Post-operative hormonal assessment showed secondary hypothyroidism and hypoadrenalism, which were both promptly treated, and a mild hypogonadism. Three months after surgery, a sellar MRI showed a persistent, increased pituitary mass (3 cm of diameter); fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) detected an increased radiopharmaceutical uptake in the sellar region. Due to the persistence of the disease and the evidence of a BRAF V600E mutation, in February 2019, the patient underwent a combined treatment with dabrafenib (a BRAF inhibitor) and trametinib (mitogen-activated extracellular signal-regulate kinase inhibitor). Sellar MRI performed 6 months later showed no evidence of mass in the sellar region. The patient was in a good clinical condition and did not complain of headaches or other symptoms; there were no significant side-effects from the anticancer therapy. After 13 months of treatment, the patient showed no recurrence of the disease on morphological imaging. Anticancer therapy was confirmed, replacement therapies with hydrocortisone and levothyroxine continued and the pituitary-gonadal axis was restored. Mormando et al. Dabrafenib-Trametinib in Pituitary Melanoma Metastasis Conclusion: This is a very interesting case, both for the rarity of the pituitary melanoma metastasis and for the singular therapeutic course carried out by the patient. This is the first case of a pituitary melanoma metastasis with BRAF mutation, successfully treated with the combination of dabrafenib and trametinib after incomplete surgical removal.

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Treatment with combined dabrafenib and trametinib in BRAFV600E-mutated metastatic malignant melanoma: a case of long-term complete response after treatment cessation

Cited by 9 publications

References 22 publications

Treatment exceeds expectations with vemurafenib monotherapy in a patient with BRAF^V600E-mutant metastatic melanoma

Treatment exceeds expectations with vemurafenib monotherapy in a patient with BRAF^V600E-mutant metastatic melanoma

Case Report: Rechallenge With BRAF and MEK Inhibitors in Metastatic Melanoma: A Further Therapeutic Option in Salvage Setting?

A Rare Case of Pituitary Melanoma Metastasis: A Dramatic and Prolonged Response to Dabrafenib-Trametinib Therapy

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Treatment with combined dabrafenib and trametinib in BRAFV600E-mutated metastatic malignant melanoma: a case of long-term complete response after treatment cessation

Cited by 9 publications

References 22 publications

Treatment exceeds expectations with vemurafenib monotherapy in a patient with BRAFV600E-mutant metastatic melanoma

Treatment exceeds expectations with vemurafenib monotherapy in a patient with BRAFV600E-mutant metastatic melanoma

Case Report: Rechallenge With BRAF and MEK Inhibitors in Metastatic Melanoma: A Further Therapeutic Option in Salvage Setting?

A Rare Case of Pituitary Melanoma Metastasis: A Dramatic and Prolonged Response to Dabrafenib-Trametinib Therapy

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Treatment exceeds expectations with vemurafenib monotherapy in a patient with BRAF^V600E-mutant metastatic melanoma

Treatment exceeds expectations with vemurafenib monotherapy in a patient with BRAF^V600E-mutant metastatic melanoma