Adjuvant and neoadjuvant treatment of melanoma
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memo https://doi.org/10.1007/s12254-020-00602-3
Adjuvant and neoadjuvant treatment of melanoma Peter Koelblinger
Received: 31 January 2020 / Accepted: 25 March 2020 © The Author(s) 2020
Summary For years, interferon alpha was the sole option in the adjuvant treatment of patients with completely resected melanoma with lymph node metastases and a high risk of disease recurrence, albeit being associated with a relatively low efficacy combined with significant toxicities. After the advent of immunotherapy and targeted therapy in locally advanced or metastatic melanoma at the beginning of the last decade, these therapeutic approaches have meanwhile also shown superior efficacy compared to previously used treatments or observation in the context of adjuvant therapy. Hence, adjuvant targeted or anti-PD1-antibody-based immunotherapy was incorporated into routine clinical practice to reduce the risk of tumor recurrence in affected patients in early 2018. Moreover, modern melanoma therapies are increasingly being investigated in a neoadjuvant setting in analogy to other solid malignancies. Considering the promising results reported so far, neoadjuvant immunotherapy might potentially become the treatment of choice in high-risk melanoma patients with macrometastatic disease in the near future. Keywords Melanoma · Adjuvant · Neoadjuvant · Targeted therapy · PD1 antibody
Introduction The emergence of targeted therapy and immunotherapy has significantly changed the treatment landscape of locally advanced or metastatic melanoma during the last decade. Unprecedented 5-year survival rates of more than 50% after combined immunotherapy P. Koelblinger, M.D. () Department of Dermatology and Allergology, Paracelsus Medical University, Müllner Hauptstraße 48, 5020 Salzburg, Austria [email protected]
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with ipilimumab and nivolumab in advanced stage melanoma are promising for affected patients, particularly when compared to historic data [1]. Nevertheless, melanoma-associated mortality remains significant. Hence, increasing efforts have been made to investigate the use of modern melanoma therapeutics earlier in the course of the disease, aiming to prevent tumor recurrence and development of metastases. In early 2018, this led to the approval of both targeted therapy and PD1 (programmed death 1)-antibody-based immunotherapy in the adjuvant treatment setting. The present review will summarize the pivotal studies published to date in this context and also focus on the next development in early medical treatment of melanoma—the neoadjuvant approach.
Adjuvant targeted therapy The Combi-AD trial investigated the combination of the BRAF inhibitor dabrafenib (75 mg twice daily) and the MEK inhibitor trametinib (2 mg once daily, D+T) compared to placebo in patients with completely resected, BRAF V600 E or K mutated American Joint Committee on Cancer (AJCC) stage III melanoma with lymph node metastases [2]. In this double blind, randomized trial, 870 patients received treatment with D+T or placebo for a total of 12 months or until the oc
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