Analysis of dermatologic events in vemurafenib-treated patients with melanoma

Mario E. Lacouture, Madeleine Duvic, Axel Hauschild, Victor G. Prieto, Caroline Robert, Dirk Schadendorf, Caroline C. Kim, Christopher J. McCormack, Patricia L. Myskowski, Olivia Spleiss, Kerstin Trunzer, Fei Su, Betty Nelson, Keith B. Nolop, Joseph F. Grippo, Richard J. Lee, Matthew J. Klimek, James L. Troy, Andrew K. Joe

Research output: Contribution to journalArticle

126 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)314-322
Number of pages9
JournalOncologist
Volume18
Issue number3
DOIs
StatePublished - Mar 1 2013

Fingerprint

Melanoma
Exanthema
Squamous Cell Carcinoma
Skin
Keratoacanthoma
PLX4032
Folliculitis
Mutation
Erythema
Dermatology
Therapeutics

Keywords

  • Cuscc
  • Dermatologic
  • Keratoacanthoma
  • Vemurafenib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Analysis of dermatologic events in vemurafenib-treated patients with melanoma. / Lacouture, Mario E.; Duvic, Madeleine; Hauschild, Axel; Prieto, Victor G.; Robert, Caroline; Schadendorf, Dirk; Kim, Caroline C.; McCormack, Christopher J.; Myskowski, Patricia L.; Spleiss, Olivia; Trunzer, Kerstin; Su, Fei; Nelson, Betty; Nolop, Keith B.; Grippo, Joseph F.; Lee, Richard J.; Klimek, Matthew J.; Troy, James L.; Joe, Andrew K.

In: Oncologist, Vol. 18, No. 3, 01.03.2013, p. 314-322.

Research output: Contribution to journalArticle

Lacouture, ME, Duvic, M, Hauschild, A, Prieto, VG, Robert, C, Schadendorf, D, Kim, CC, McCormack, CJ, Myskowski, PL, Spleiss, O, Trunzer, K, Su, F, Nelson, B, Nolop, KB, Grippo, JF, Lee, RJ, Klimek, MJ, Troy, JL & Joe, AK 2013, 'Analysis of dermatologic events in vemurafenib-treated patients with melanoma', Oncologist, vol. 18, no. 3, pp. 314-322. https://doi.org/10.1634/theoncologist.2012-0333
Lacouture, Mario E. ; Duvic, Madeleine ; Hauschild, Axel ; Prieto, Victor G. ; Robert, Caroline ; Schadendorf, Dirk ; Kim, Caroline C. ; McCormack, Christopher J. ; Myskowski, Patricia L. ; Spleiss, Olivia ; Trunzer, Kerstin ; Su, Fei ; Nelson, Betty ; Nolop, Keith B. ; Grippo, Joseph F. ; Lee, Richard J. ; Klimek, Matthew J. ; Troy, James L. ; Joe, Andrew K. / Analysis of dermatologic events in vemurafenib-treated patients with melanoma. In: Oncologist. 2013 ; Vol. 18, No. 3. pp. 314-322.
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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.",
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AU - Hauschild, Axel

AU - Prieto, Victor G.

AU - Robert, Caroline

AU - Schadendorf, Dirk

AU - Kim, Caroline C.

AU - McCormack, Christopher J.

AU - Myskowski, Patricia L.

AU - Spleiss, Olivia

AU - Trunzer, Kerstin

AU - Su, Fei

AU - Nelson, Betty

AU - Nolop, Keith B.

AU - Grippo, Joseph F.

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N2 - 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.

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