pyrimidinones and Acneiform-Eruptions

The MEK inhibitor trametinib is currently undergoing clinical trials as the treatment of metastatic melanoma both alone and in combination with the BRAF inhibitor dabrafenib. One of the most frequent side-effects associated with its use as a single agent is the development of acneiform eruptions. These eruptions seem to be reduced when dosed in combination with dabrafenib.. To investigate the prevalence of acneiform eruptions in patients taking the MEK inhibitor trametinib, both alone and in combination with dabrafenib.. All patients enrolled in the trametinib alone (n = 13) or trametinib and dabrafenib combination (n = 30) clinical trials at a single site underwent a retrospective file review. The development and management of acne or acneiform eruptions was noted.. In total, 77% of the trametinib group developed an acneiform eruption on the trial, while only 10% developed acneiform lesions in the combination trial. The patients were treated with oral doxycycline, topical antibiotics or topical antiseptic washes, with a good response. However the condition recurred if these treatments were ceased and the patient was still on trametinib therapy.. The MEK inhibitor trametinib is associated with the development of acneiform eruptions. When combined with dabrafenib the frequency of this side-effect is reduced.

Topics: Acneiform Eruptions; Administration, Cutaneous; Adult; Aged; Anti-Bacterial Agents; Anti-Infective Agents, Local; Antineoplastic Combined Chemotherapy Protocols; Clindamycin; Clinical Trials as Topic; Doxycycline; Drug Eruptions; Female; Humans; Imidazoles; Male; Melanoma; Middle Aged; Oximes; Protein Kinase Inhibitors; Pyridones; Pyrimidinones; Retrospective Studies; Skin Neoplasms; Triclosan

BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) increase survival in BRAF mutant metastatic melanoma patients; however, they induce a well-known spectrum of cutaneous side effects during treatment. Whereas the BRAFi dabrafenib induces cutaneous squamous cell carcinomas and verrucal keratosis, the MEKi trametinib frequently induces acneiform eruptions that are reversible after drug discontinuation. Furthermore, when dabrafenib and trametinib are used in combination, there are fewer cutaneous toxicities. We report a patient with BRAF mutant metastatic melanoma treated with the BRAFi/MEKi combination therapy who developed an acneiform eruption after treatment discontinuation rather than during active therapy. Moreover, the eruption resolved when the combination treatment was reintroduced and recurred after increasing the dose of trametinib. The eruption may be explained by the longer half-life of trametinib (4.5 days) compared with dabrafenib (5.2 h). This is the first case reported with this particular side effect induced after stopping the treatment and could become more frequent as the BRAFi/MEKi combination of drugs is more frequently prescribed.

Topics: Acneiform Eruptions; Adrenal Cortex Hormones; Adult; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Drug Administration Schedule; Fatal Outcome; Female; Fever; Humans; Imidazoles; Melanoma; Mutation; Neoplasm Metastasis; Oximes; Proto-Oncogene Proteins B-raf; Pyridones; Pyrimidinones; Skin Neoplasms; Time Factors; Treatment Outcome

Topics: Acneiform Eruptions; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Imidazoles; Indoles; MAP Kinase Kinase Kinases; Melanoma; Oximes; Proto-Oncogene Proteins B-raf; Pyridones; Pyrimidinones; Skin Neoplasms; Sulfonamides; Vemurafenib