Abstract
Background
During 2011 and 2014, new treatment modalities like tyrosine kinase inhibitors and checkpoint inhibitors were introduced into the therapy of metastatic melanoma. This study addresses the question whether overall survival (OS) of metastatic melanoma patients has already been improved in 441 patients diagnosed with metastatic melanoma between 2011 and 2014 in the real-world setting at the University Hospital Tuebingen.
Methods
All patients were documented with their different therapies by the CMMR and followed up until March 2016. Survival probabilities were calculated by Kaplan–Meier estimators, and log-rank tests were used to evaluate significances. Hazard ratios were estimated by Cox regression analysis for survival probabilities and prognostic factors in stage IV melanoma.
Results
Best OS was observed in patients (n = 93) treated by metastasectomy as primary treatment with the intention to completely excise all metastases (3-year OS 61%). OS for patients with first-line systemic treatment (n = 258) was unfavorable in general (3-year OS 23%). Of those, the most favorable outcome was observed in patients without brain metastasis and treated with immunotherapy (mostly ipilimumab), as first-line treatment (median OS 35 months, 3-year OS 43%). In case of brain metastases, patients with targeted therapy had a better OS (median 14 months) than patients with ipilimumab treatment (median 7 months). Among all patients with first-line systemic treatment, outcome of patients diagnosed in the years 2013/2014, compared to 2011 and 2012, showed an improved survival. Three-year OS for patients that entered stage IV in 2013/2014 was 37% compared to those that entered stage IV in 2011 (18%) and 2012 (20%).
Conclusion
The analysis of real-world data of treatment of metastatic melanoma showed an improvement of OS with both immunotherapy and targeted therapy. In case of cerebral metastasis, patients treated with targeted therapy showed a longer median OS than patients treated with ipilimumab.
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References
Balch CM, Gershenwald JE, Soong SJ et al (2009) Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 27:6199–6206
Chapman PB, Hauschild A, Robert C et al (2011) Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364:2507–2516
Dummer R, Hauschild A, Guggenheim M et al (2012) Cutaneous melanoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 23:vii86–vii91
Dummer R, Goldinger SM, Turtschi CP et al (2014) Vemurafenib in patients with BRAF(V600) mutation-positive melanoma with symptomatic brain metastases: final results of an open-label pilot study. Eur J cancer 50:611–621 (Oxford, England: 1990
Eigentler TK, Caroli UM, Radny P et al (2003) Palliative therapy of disseminated malignant melanoma: a systematic review of 41 randomised clinical trials. Lancet Oncol 4:748–759
Hauschild A, Grob JJ, Demidov LV et al (2012) Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet 380:358–365 (London, England)
Larkin J, Ascierto PA, Dréno B et al (2014) Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med 371:1867–1876
Leeneman B, Franken MG, Jochems A et al (2015) Improved survival in patients with advanced melanoma in real-world clinical practice: first results of the Dutch melanoma treatment registry. Value in Health: Journal Int Soc Pharmacoecon Outcomes Res 18:A440–A441
Long GV, Trefzer U, Davies MA et al (2012) Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial. Lancet Oncol 13:1087–1095
Long GV, Stroyakovskiy D, Gogas H et al (2014) Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med 371:1877–1888
Long GV, Stroyakovskiy D, Gogas H et al (2015) Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet 386:444–451 (London, England)
Margolin K (2012) Ipilimumab in a phase II trial of melanoma patients with brain metastases. Oncoimmunology 1:1197–1199
Niezgoda A, Niezgoda P, Czajkowski R (2015) Novel approaches to treatment of advanced melanoma: a review on targeted therapy and immunotherapy. BioMed Res Int 2015:851387
Pflugfelder A, Eigentler TK, Keim U et al (2011) Effectiveness of carboplatin and paclitaxel as first- and second-line treatment in 61 patients with metastatic melanoma. PLoS ONE 6:e16882
Pflugfelder A, Kochs C, Blum A et al (2013) Malignant melanoma S3-guideline diagnosis, therapy and follow-up of melanoma. Journal der Deutschen Dermatologischen Gesellschaft, J Ger Soc Dermatol JDDG 11 Suppl 6(1–116):111–126
Robert C, Thomas L, Bondarenko I et al (2011) Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 364:2517–2526
Robert C, Long GV, Brady B et al (2015a) Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 372:320–330
Robert C, Schachter J, Long GV et al (2015b) Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 372:2521–2532
Thompson JA, Hamid O, Minor D et al (2012) Ipilimumab in treatment-naive and previously treated patients with metastatic melanoma: retrospective analysis of efficacy and safety data from a phase II trial. J Immunother 35:73–77 (Hagerstown, Md.: 1997)
Tsao H, Atkins MB, Sober AJ (2004) Management of cutaneous melanoma. N Engl J Med 351:998–1012
Weide B, Elsasser M, Buttner P et al (2012) Serum markers lactate dehydrogenase and S100B predict independently disease outcome in melanoma patients with distant metastasis. Br J Cancer 107:422–428
Wong DJ, Ribas A (2016) Targeted therapy for melanoma. Cancer Treat Res 167:251–262
Zaretsky JM, Garcia-Diaz A, Shin DS et al (2016) Mutations associated with acquired resistance to pd-1 blockade in melanoma. N Engl J Med 375:819–829
Authors’ contributions
AF contributed to literature search, figures, data collection, data analysis, data interpretation and writing; FE and TKE were involved in data collection, data analysis, data interpretation and writing; TA was involved in data collection, data analysis and data interpretation; UK contributed to data analysis and figures; CG was involved in data interpretation and writing.
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Andrea Forschner reports personal fees from BMS, MSD, Novartis, Roche, outside the submitted work. Claus Garbe reports personal fees from Amgen, LEO, MSD, Philogen, and grants and personal fees from BMS, Novartis, Roche, outside the submitted work. Thomas Kurt Eigentler reports personal fees from Amgen, BMS, MSD, Novartis, Roche, outside the submitted work. Felicitas Eichner, Teresa Amaral and Ulrike Keim have no conflict of interest.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the local ethics committee of the University of Tuebingen (Reference Number 676/2016BO2).
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Informed consent was obtained from all patients included in this study.
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Forschner, A., Eichner, F., Amaral, T. et al. Improvement of overall survival in stage IV melanoma patients during 2011–2014: analysis of real-world data in 441 patients of the German Central Malignant Melanoma Registry (CMMR). J Cancer Res Clin Oncol 143, 533–540 (2017). https://doi.org/10.1007/s00432-016-2309-y
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DOI: https://doi.org/10.1007/s00432-016-2309-y