PMID- 32875931 OWN - NLM STAT- MEDLINE DCOM- 20220609 LR - 20220617 IS - 1471-1753 (Electronic) IS - 0954-6634 (Linking) VI - 33 IP - 3 DP - 2022 May TI - Long-term vemurafenib therapy in advanced melanoma patients: cutaneous toxicity and prognostic implications. PG - 1368-1375 LID - 10.1080/09546634.2020.1817838 [doi] AB - BACKGROUND: The introduction of targeted therapies for the treatment of BRAF-mutated metastatic melanoma was associated with different cutaneous adverse events (AEs). OBJECTIVES: To describe the type, frequency and severity of cutaneous AEs related to vemurafenib; to understand the association between AEs and vemurafenib efficacy in terms of median overall survival (OS) and median progression-free survival (PFS); to identify molecular characteristics of long-term responders. METHODS: This observational, retrospective, monocentric study included all consecutive patients with unresectable stage III or stage IV melanoma and BRAF V600E mutation that started treatment with vemurafenib between May 2012 and May 2014. RESULTS: 62 patients with a median age of 56 years (range 26-82) were enrolled and received vemurafenib for a median period of 7.9 months (range 0.8-63.7). Among them, 45 patients presented at least one skin AE, 12 reduced the dosage due to cutaneous toxicity, and only one firstly reduced and after stopped the therapy. No specific molecular biomarkers were detected in long-term survivors. CONCLUSIONS: Among long-term survivors, skin AEs seem to be less frequent and less severe. Results on multivariable analysis revealed that the presence of at least one G2 toxicity is a protective factor considering PFS, but not in terms of OS. FAU - Mandel, Victor Desmond AU - Mandel VD AUID- ORCID: 0000-0003-0682-6148 AD - Skin Cancer Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy. AD - Dermatology Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy. FAU - Medri, Matelda AU - Medri M AD - Skin Cancer Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy. FAU - Manganoni, Ausilia Maria AU - Manganoni AM AD - Department of Dermatology, Spedali Civili di Brescia, Brescia, Italy. FAU - Pavoni, Laura AU - Pavoni L AD - Department of Dermatology, Spedali Civili di Brescia, Brescia, Italy. FAU - De Rosa, Francesco AU - De Rosa F AD - Immunotherapy, Cell Therapy and Biobank, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy. FAU - Ribero, Simone AU - Ribero S AUID- ORCID: 0000-0002-0098-1406 AD - Dermatologic Clinic, Department of Medical Sciences, University of Turin, Turin, Italy. FAU - Foca, Flavia AU - Foca F AUID- ORCID: 0000-0002-5529-4769 AD - Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy. FAU - Andreis, Daniele AU - Andreis D AUID- ORCID: 0000-0001-6686-5662 AD - Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy. FAU - Mazzoni, Laura AU - Mazzoni L AD - Skin Cancer Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy. FAU - Magi, Serena AU - Magi S AD - Skin Cancer Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy. FAU - Farnetani, Francesca AU - Farnetani F AUID- ORCID: 0000-0001-7088-9077 AD - Dermatology Unit, Surgical, Medical and Dental Department of Morphological Sciences related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy. FAU - Palla, Marco AU - Palla M AUID- ORCID: 0000-0001-8901-0974 AD - Unit of Melanoma, Cancer Immunotherapy & Innovative Therapies Unit, Istituto Nazionale Tumori "Fondazione G. Pascale", Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Naples, Italy. FAU - Ulivi, Paola AU - Ulivi P AUID- ORCID: 0000-0002-4334-9662 AD - Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy. FAU - Stanganelli, Ignazio AU - Stanganelli I AD - Skin Cancer Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola, Italy. AD - Dermatology Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy. LA - eng PT - Journal Article PT - Observational Study DEP - 20200909 PL - England TA - J Dermatolog Treat JT - The Journal of dermatological treatment JID - 8918133 RN - 0 (Sulfonamides) RN - 207SMY3FQT (Vemurafenib) RN - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Humans MH - *Melanoma/drug therapy/genetics/pathology MH - Middle Aged MH - Mutation MH - Prognosis MH - Proto-Oncogene Proteins B-raf/genetics MH - Retrospective Studies MH - *Skin Diseases MH - *Skin Neoplasms/drug therapy/genetics MH - Sulfonamides/adverse effects MH - Vemurafenib/adverse effects OTO - NOTNLM OT - Melanoma OT - cancer survivors OT - drug-related side effects and adverse reactions OT - long term adverse effects OT - long-term care OT - melanoma, cutaneous malignant OT - proto-oncogene proteins B-raf OT - skin neoplasms OT - survivors OT - vemurafenib EDAT- 2020/09/03 06:00 MHDA- 2022/06/10 06:00 CRDT- 2020/09/03 06:00 PHST- 2020/09/03 06:00 [pubmed] PHST- 2022/06/10 06:00 [medline] PHST- 2020/09/03 06:00 [entrez] AID - 10.1080/09546634.2020.1817838 [doi] PST - ppublish SO - J Dermatolog Treat. 2022 May;33(3):1368-1375. doi: 10.1080/09546634.2020.1817838. Epub 2020 Sep 9.