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Erschienen in: memo - Magazine of European Medical Oncology 3/2014

01.09.2014 | special report

Long-term tolerability of the BRAF inhibitor vemurafenib in patients with metastatic melanoma: current study data and real-life observations

verfasst von: Cathrin Balmelli, MD, Michael Mark, MD, Christian Spirig, MD, Vito Spataro, MD, Stefanie Pederiva, MD, Christian Monnerat, MD, Prof. Alfred Zippelius, Andreas Wicki, MD, PhD

Erschienen in: memo - Magazine of European Medical Oncology | Ausgabe 3/2014

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Abstract

Vemurafenib is a targeted therapy against metastatic melanoma. It specifically inhibits the V600 mutated BRAF kinase in the mitogen-activated protein kinase pathway. Only limited data are available on long-term tolerability and efficacy of this drug. Here, we report and discuss six patients from our own clinical practice who were treated with vemurafenib for 16–27 months. Overall, these long-term responders tolerated vemurafenib well during the prolonged period of therapy. Most of the side-effects occurred during the first 6 months of treatment and were transient. The most common persistent side-effect was phototoxicity, which was manageable by precautionary measures or with dose reduction. Interestingly, even permanent dose reductions of 50 % of the standard dose did not abrogate long lasting remissions but improved tolerability, which is a prerequisite of long-term therapy. In addition to our own clinical experience, this article reviews current study results regarding the tolerability and efficacy of long-term vemurafenib therapy.
Literatur
1.
Zurück zum Zitat Agarwala SS. Current systemic therapy for metastatic melanoma. Expert Rev Anticancer Ther. 2009;9:587–95. doi:10.1586/era.09.25.PubMedCrossRef Agarwala SS. Current systemic therapy for metastatic melanoma. Expert Rev Anticancer Ther. 2009;9:587–95. doi:10.1586/era.09.25.PubMedCrossRef
2.
Zurück zum Zitat Chiarion Sileni V, Nortilli R, Aversa SM, et al. Phase II randomized study of dacarbazine, carmustine, cisplatin and tamoxifen versus dacarbazine alone in advanced melanoma patients. Melanoma Res. 2001;11(2):189–96.PubMedCrossRef Chiarion Sileni V, Nortilli R, Aversa SM, et al. Phase II randomized study of dacarbazine, carmustine, cisplatin and tamoxifen versus dacarbazine alone in advanced melanoma patients. Melanoma Res. 2001;11(2):189–96.PubMedCrossRef
3.
Zurück zum Zitat Chapman PB, Einhorn LH, Meyers ML, et al. Phase III multicenter randomized trial of the dartmouth regimen versus dacarbazine in patients with metastatic melanoma. J Clin Oncol. 1999;17(9):2745–51.PubMed Chapman PB, Einhorn LH, Meyers ML, et al. Phase III multicenter randomized trial of the dartmouth regimen versus dacarbazine in patients with metastatic melanoma. J Clin Oncol. 1999;17(9):2745–51.PubMed
4.
Zurück zum Zitat Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23. doi:10.1056/NEJMoa1003466.PubMedCrossRefPubMedCentral Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23. doi:10.1056/NEJMoa1003466.PubMedCrossRefPubMedCentral
5.
Zurück zum Zitat Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517–26. doi:10.1056/NEJMoa1104621.PubMedCrossRef Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517–26. doi:10.1056/NEJMoa1104621.PubMedCrossRef
6.
Zurück zum Zitat Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417:949–54.PubMedCrossRef Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417:949–54.PubMedCrossRef
7.
Zurück zum Zitat Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–16. doi:10.1056/NEJMoa1103782.PubMedCrossRefPubMedCentral Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–16. doi:10.1056/NEJMoa1103782.PubMedCrossRefPubMedCentral
8.
Zurück zum Zitat Sosman JA, Kim KB, Schuchter L, et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med. 2012;366(8):707–14. doi:10.1056/NEJMoa1112302.PubMedCrossRefPubMedCentral Sosman JA, Kim KB, Schuchter L, et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med. 2012;366(8):707–14. doi:10.1056/NEJMoa1112302.PubMedCrossRefPubMedCentral
9.
Zurück zum Zitat Tsai J, Lee JT, Wang W, et al. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc Natl Acad Sci USA. 2008;105(8):3041–6. doi:10.1073/pnas.0711741105.PubMedCrossRefPubMedCentral Tsai J, Lee JT, Wang W, et al. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc Natl Acad Sci USA. 2008;105(8):3041–6. doi:10.1073/pnas.0711741105.PubMedCrossRefPubMedCentral
10.
Zurück zum Zitat Swiss Agency for Therapeutic Products, Medicinal Product Information, Zelboraf 240 mg film-coated tablets. Available at: www.swissmedicinfo.ch. Accessed 31 Oct 2013. Swiss Agency for Therapeutic Products, Medicinal Product Information, Zelboraf 240 mg film-coated tablets. Available at: www.​swissmedicinfo.​ch. Accessed 31 Oct 2013.
11.
Zurück zum Zitat Hauschild A, McArthur G, Robert C, et al. Vemurafenib improves overall survival compared with dacarbazine in advanced BRAF V600-mutated melanoma: updated results from a phase 3 randomized, multicenter trial. Poster and Abstract at the 10th International Meeting of the Society for Melanoma Research; November 17–20, 2013; Philadelphia. Hauschild A, McArthur G, Robert C, et al. Vemurafenib improves overall survival compared with dacarbazine in advanced BRAF V600-mutated melanoma: updated results from a phase 3 randomized, multicenter trial. Poster and Abstract at the 10th International Meeting of the Society for Melanoma Research; November 17–20, 2013; Philadelphia.
12.
Zurück zum Zitat Kim K, Amaravadi R, Flaherty K, et al. Significant long-term survival benefit demonstrated with vemurafenib in ongoing phase I study. Poster and Abstract at the Society for Melanoma Research 2012 Congress; November 8–11, 2012; Hollywood, CA, USA. Kim K, Amaravadi R, Flaherty K, et al. Significant long-term survival benefit demonstrated with vemurafenib in ongoing phase I study. Poster and Abstract at the Society for Melanoma Research 2012 Congress; November 8–11, 2012; Hollywood, CA, USA.
13.
14.
Zurück zum Zitat Larkin J, Del Vecchio M, Ascierto PA, et al. Vemurafenib in patients with BRAFV600 mutated metastatic melanoma: an open-label, multicenter, safety study. Lancet Oncol. 2014;15:436–44. doi:10.1016/S1470-2045(14)70051-8. Larkin J, Del Vecchio M, Ascierto PA, et al. Vemurafenib in patients with BRAFV600 mutated metastatic melanoma: an open-label, multicenter, safety study. Lancet Oncol. 2014;15:436–44. doi:10.1016/S1470-2045(14)70051-8.
15.
Zurück zum Zitat Dummer R, Goldinger SM, Turtschi CP, et al. Vemurafenib in patients with BRAFV600 mutation-positive melanoma with symptomatic brain metastases: Final results of an open-label pilot study. Eur J Cancer. 2013;50(3):611–21. doi:10.1016/j.ejca.2013.11.002. Dummer R, Goldinger SM, Turtschi CP, et al. Vemurafenib in patients with BRAFV600 mutation-positive melanoma with symptomatic brain metastases: Final results of an open-label pilot study. Eur J Cancer. 2013;50(3):611–21. doi:10.1016/j.ejca.2013.11.002.
16.
Zurück zum Zitat Kefford R, Maio M, Arance A, et al. Vemurafenib in metastatic melanoma patients with brain metastasis: An open-label, single-arm, phase 2, multicenter study. Poster and Abstract at the Society for Melanoma Research 2013 Congress; November 17–20, 2013; Philadelphia, PA, USA. Kefford R, Maio M, Arance A, et al. Vemurafenib in metastatic melanoma patients with brain metastasis: An open-label, single-arm, phase 2, multicenter study. Poster and Abstract at the Society for Melanoma Research 2013 Congress; November 17–20, 2013; Philadelphia, PA, USA.
17.
Zurück zum Zitat Su F, Viros A, Milagre C, et al. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med. 2012;366(3):207–15. doi:10.1056/NEJMoa1105358.PubMedCrossRefPubMedCentral Su F, Viros A, Milagre C, et al. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med. 2012;366(3):207–15. doi:10.1056/NEJMoa1105358.PubMedCrossRefPubMedCentral
18.
Zurück zum Zitat Flaherty KT, Infante JR, Daud A, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 Mutations. N Engl J Med. 2012;367(18):1694–703. doi:10.1056/NEJMoa1210093.PubMedCrossRefPubMedCentral Flaherty KT, Infante JR, Daud A, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 Mutations. N Engl J Med. 2012;367(18):1694–703. doi:10.1056/NEJMoa1210093.PubMedCrossRefPubMedCentral
Metadaten
Titel
Long-term tolerability of the BRAF inhibitor vemurafenib in patients with metastatic melanoma: current study data and real-life observations
verfasst von
Cathrin Balmelli, MD
Michael Mark, MD
Christian Spirig, MD
Vito Spataro, MD
Stefanie Pederiva, MD
Christian Monnerat, MD
Prof. Alfred Zippelius
Andreas Wicki, MD, PhD
Publikationsdatum
01.09.2014
Verlag
Springer Vienna
Erschienen in
memo - Magazine of European Medical Oncology / Ausgabe 3/2014
Print ISSN: 1865-5041
Elektronische ISSN: 1865-5076
DOI
https://doi.org/10.1007/s12254-014-0156-6

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