Cardiac tamponade induced by dabrafenib and trametinib combination therapy for melanoma

Abstract

Rationale:BRAF and MEK inhibitors (BRAF/MEKi) are targeted therapy for proto-oncogene BRAF mutated metastatic unresectable melanoma. Compared to monotherapy, an increased cardiovascular toxicity is reported with the combination of Dabrafenib and Trametinib. This case report documents Grade 4 cardiac treatment emergent adverse effect of pericardial effusion and cardiac tamponade induced by this combination therapy.Patient concerns:A 52 year old man presented with clinical stage II unresectable melanoma with BRAF V600E mutation, was initiated on treatement with Dabrafenib and Trametinib. He complained of generalised edema and increased his weight by 27 kg. This progressed to shortness of breath and he underwent echocardiogram which revealed cardiac tamponade.Diagnoses:Emergent pericardiocentesis was performed. No definited pathology was demonstrated in laboratory analysis of pericardial fluid. Re- initiating treatment resulted in cardiac tamponade and pericardiotomy was performed by video-assisted thoracic surgical (VATS). Pericardial biopsy revealed nonspecific chronic inflammation.Interventions:Discontinuation of treatment with Dabrafenib and Trametinib and diuretics resolved peripheral edema. Cardiac function normalized after pericardiocentesis and pericardiotomy.Outcomes:Treatment with Dabrafenib and Trametinib caused significant peripheral edema and pericardial effusion resulting in cardiac tamponade. Naranjo score suggests probable association of treatment induced pericardial effusion and cardiac tamponade.Lessons:This is the first documented report of pericardial effusion and cardiac tamponade induced by Dabrafenib and Trametinib. Cardiac toxicity of BRAF/MEK inhibitors is rare but clinicans must monitor for treatment emergent adverse effects.

Dabrafenib and trametinib therapy in an elderly patient with non‐small cell lung cancer harboring the BRAF V600E mutation

“…In addition, when peripheral edema is observed, clinicians must always exclude a reduction in the left ventricular ejection fraction and cardiac tamponade using ultrasound cardiography. 22 Liver dysfunction did not occur in the present case; thus, hypoalbuminemia was not derived from liver toxicity. As the ability to assimilate nutrients decreases, tumor-induced inflammation increases, and the clearing of necrotic tumor cells from the body after durable treatment becomes less effective with age, and it might be necessary to monitor patients for chemotherapyinduced hypoalbuminemia and peripheral edema when chemotherapy is administered to "oldest old" patients.…”

“…However, in the present case the peripheral edema caused by hypoalbuminemia triggered a decline in the patient's QOL, which could be intolerable for some patients. In addition, when peripheral edema is observed, clinicians must always exclude a reduction in the left ventricular ejection fraction and cardiac tamponade using ultrasound cardiography 22 . Liver dysfunction did not occur in the present case; thus, hypoalbuminemia was not derived from liver toxicity.…”

Trametinib and dabrafenib induced rhabdomyolysis, renal failure, and visual loss. Report of one case

“…Trametinib alone or together with dabrafenib is successfully applied for BRAF-mutated, metastasizing melanoma 1 . If trametinib is given alone, the tumor tends to be- [11] No Cardiac Heart failure [12] No Cardiac tamponade [13] No Arterial hypertension [14] No Heart failure [15] Yes (probNP ↑) Granulomatous myocarditis [16] No Dermatological Squamous cell carcinoma [12] No Panniculitis [17] No Vitiligo-like lesion [17] No Xantho-granulomatous lesions [18] No Erythema nodosum [8] No Keratitis sicca [8] No Histiocytoid sweets syndrome [19] No Pyoderma gangraenosum [20] No Localised hyperkeratosis [21] No Verrucous keratosis [21] No Keratoakanthoma [21] No…”