Psoriasis pustulosa asociada a inhibidores BRAF para el tratamiento del melanoma metastásico / Pustular psoriasis with BRAF inhibitors to treat metastatic melanoma

La inhibición dirigida de BRAF con vemurafenib y dabrafenib ha demostrado ser una opción de tratamiento del melanoma metastásico con mutación BRAF-V600E. Sin embargo, los eventos adversos cutáneos son frecuentes con los inhibidores de BRAF, siendo la psoriasis una complicación rara. Presentamos un caso de psoriasis pustulosa palmoplantar en un hombre adulto con melanoma metastásico tratado con ambos inhibidores de BRAF, de forma secuencial. Fue incluso necesario el tratamiento con corticoides sistémicos y apremilast para controlar la sintomatología. Hasta la fecha, sólo se ha descrito en la literatura un caso de psoriasis asociada a dabrafenib. Postulamos que la elevación del factor de necrosis tumoral alfa (TNF-a) y la activación paradójica de la vía de la proteína quinasa activada por mitógenos (MAPK) debido a la inhibición de BRAF pueden ser responsables de este caso. Se necesitan más estudios para dilucidar más a fondo los mecanismos inmunopatógenos detrás de este evento adverso

Targeted BRAF inhibition with vemurafenib and dabrafenib has proven to be a useful tool in the treatment of metastatic melanoma with BRAF-V600E mutation. While cutaneous adverse events are prevalent with BRAF inhibition, psoriasis is a rare complication. We report a case of palmoplantar pustular psoriasis in an adult man with metastatic melanoma treated with both BRAF inhibitors, sequentially. Systemic corticosteroids and apremilast were required to control symptomatology. To date, a case has been described in the literature of psoriasis associated with dabrafenib. We postulate that the elevation of tumor necrosis factor-alpha (TNF-a) and the paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway due to BRAF inhibition may be responsible for this case. More studies are needed to further elucidate the immunopathogenic mechanisms behind this adverse event

FR-Novedades en la terapia adyuvante del melanoma cutáneo avanzado / Good News on Adjuvant Therapy for Advanced Cutaneous Melanoma

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Doublet BRAF/MEK inhibition versus single-agent BRAF inhibition in the management of BRAF-mutant advanced melanoma, biological rationale and meta-analysis of published data

BACKGROUND: We executed a comparative systematic review and meta-analysis of the efficacy and toxicity of doublet BRAF/MEK inhibition versus single-agent BRAF inhibitor in the management of BRAF-mutant advanced melanoma. METHODS: Eligible studies included prospective studies evaluating doublet regimens versus BRAF-inhibitor monotherapy for the management of BRAF-mutant advanced melanoma. RESULTS: Our search strategy yielded 200 potentially relevant citations from searched databases. After preclusion of ineligible studies, four studies were included in the final analysis. Efficacy analyses demonstrate that BRAF/MEK inhibition strategy is associated with a significant improvement in ORR [OR 1.35; 95 % CI (1.16, 1.58); P = 0.0002], PFS [HR 0.56; 95 % CI (0.49, 0.64); P < 0.00001] and OS [HR 0.70; 95 % CI (0.58, 0.84); P = 0.0001]. Moreover, this combination is associated with a higher RR for diarrhea [1.30; 95 % CI (1.30, 1.49); P = 0.0002], decreased ejection fraction [4.63; 95 % CI (2.56, 8.37); P = <0.00001], acneiform dermatitis [1.61; 95 % CI (1.03, 2.53); P = 0.04] and pyrexia [1.98; 95 % CI (1.72, 2.27); P < 0.00001]. CONCLUSIONS: Our meta-analysis has demonstrated that combination of MEK/BRAF inhibitors is associated with higher ORR, PFS and OS. However, this comes at the expense of a higher risk of selected toxicities

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