Analysis of dermatologic events in vemurafenib-treated patients with melanoma Journal Article
| Authors: | Lacouture, M. E.; Duvic, M.; Hauschild, A.; Prieto, V. G.; Robert, C.; Schadendorf, D.; Kim, C. C.; McCormack, C. J.; Myskowski, P. L.; Spleiss, O.; Trunzer, K.; Su, F.; Nelson, B.; Nolop, K. B.; Grippo, J. F.; Lee, R. J.; Klimek, M. J.; Troy, J. L.; Joe, A. K. |
| Article Title: | Analysis of dermatologic events in vemurafenib-treated patients with melanoma |
| Abstract: | Background. Vemurafenib has been approved for the treatment of patients with advanced BRAFV600E-mutant melanoma. This report by the Vemurafenib Dermatology Working Group presents the characteristics of dermatologic adverse events (AEs) that occur in vemurafenib-treated patients, including cutaneous squamous cell carcinoma (cuSCC). Methods. Dermatologic AEs were assessed from three ongoing trials of BRAFV600E mutation-positive advanced melanoma. Histologic central review and genetic characterization were completed for a subset of cuSCC lesions. Results. A total of 520 patients received vemurafenib. The most commonly reported AEs were dermatologic AEs, occurring in 92%-95% of patients. Rash was the most common AE (64%-75% of patients), and the most common types were rash not otherwise specified, erythema, maculopapular rash, and folliculitis. Rash development did not appear to correlate with tumor response. Photosensitivity occurred in 35%-63% of patients, and palmar-plantar erythrodysesthesia (PPE) occurred in 8%-10% of patients. The severity of rash, photosensitivity, and PPE were mainly grade 1 or 2. In all, 19%-26% of patients developed cuSCC, mostly keratoacanthomas (KAs). The majority of patients with cuSCC continued therapy with outdoser eduction after resection.Genetic analysisof 29 cuSCC/ KA samples demonstrated HRAS mutations in 41%. Conclusions. Dermatologic AEs associated with vemurafenib treatment in patients with melanoma were generally manageable with supportive care measures. Dose interruptions and/or reductions were required in <10% of patients. © AlphaMed Press 2013. |
| Keywords: | adolescent; adult; human tissue; treatment outcome; aged; aged, 80 and over; middle aged; young adult; oncoprotein; major clinical study; sequence analysis; mutation; disease course; raf protein; drug dose reduction; drug withdrawal; clinical trials as topic; genetic analysis; dacarbazine; melanoma; quality of life; pain; skin neoplasms; randomized controlled trials as topic; steroid; mutational analysis; skin carcinoma; drug dose escalation; rash; maculopapular rash; prednisolone; disease severity; sulfonamides; nonsteroid antiinflammatory agent; erythema; neoplasms, second primary; indoles; hand foot syndrome; b raf kinase; skin diseases; photosensitivity; antihistaminic agent; sunburn; keratoacanthoma; randomized controlled trial (topic); phase 2 clinical trial (topic); phase 3 clinical trial (topic); phase 1 clinical trial (topic); dermatologic; 4 aminobutyric acid; skin abrasion; phototoxicity; keratolytic agent; folliculitis; vemurafenib; darier disease; cuscc |
| Journal Title: | The Oncologist |
| Volume: | 18 |
| Issue: | 3 |
| ISSN: | 1083-7159 |
| Publisher: | Oxford University Press |
| Date Published: | 2013-01-01 |
| Start Page: | 314 |
| End Page: | 322 |
| Language: | English |
| PROVIDER: | scopus |
| PMCID: | PMC3607529 |
| PUBMED: | 23457002 |
| DOI: | 10.1634/theoncologist.2012-0333 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 May 2013" - "CODEN: OCOLF" - ":doi 10.1634/theoncologist.2012-0333" - ": Chemicals/CAS4 aminobutyric acid, 28805-76-7, 56-12-2; dacarbazine, 4342-03-4; prednisolone, 50-24-8; vemurafenib, 918504-65-1" - "Source: Scopus" |
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