A New Era of Proactive Melanoma Therapy: Hit Hard, Hit Early

L. Haas; T. Wiesner; A. C. Obenauf


The British Journal of Dermatology. 2018;178(4):817-820. 

In This Article

Abstract and Introduction


The therapeutic strategies for patients with melanoma have undergone a paradigm shift in recent years. Targeted and immunotherapies have made their way into clinical practice and have largely replaced cytotoxic chemotherapies (Figure 1). In light of this shift to rational and mechanism–based therapies, we discuss in this Editorial three melanoma trials, recently published in The New England Journal of Medicine (NEJM).[1–3]

Figure 1.

Comparison of targeted and immunotherapies.

The first of these three trials affirms the central role of immunotherapy for patients with metastasized melanoma. In this study, Wolchok et al.[1] report a 3–year overall survival rate of > 50% for patients with unresectable melanoma using immunotherapy with nivolumab. The other two studies investigate the clinical value of targeted and immunotherapies as adjuvant treatment strategies for patients with fully resected disease.[2,3] Weber et al.[2] show that adjuvant immunotherapy with nivolumab, compared with ipilimumab, resulted in significantly longer recurrence–free survival and less adverse events. Long et al.[3] analysed adjuvant targeted therapy with dabrafenib plus trametinib, and report a 53% reduced risk of relapse in the treatment vs. the placebo group at a median follow–up of 2·8 years.

In the past, adjuvant therapies for melanoma were mainly based on interferon or ipilimumab, and were often characterized by low efficacy and severe adverse events.[4] However, these new results using targeted and immunotherapies revive adjuvant strategies and foreshadow a new era of proactive cancer therapy. The underlying rationale is that cancer cells often disseminate to the lymph nodes and distant organs before the primary tumour is excised.[5] Adjuvant therapies aim to eradicate these disseminated cells early to prevent the development of clinically detectable metastasis.

Shifting the start of therapy from a metastatic setting with millions or billions of tumour cells to an adjuvant setting with only a few disseminated tumour cells present, could make an important difference (Figure 2). The probability of cancer cells acquiring drug resistance – one of the central problems in oncology – should be lower in an adjuvant setting because of the reduced tumour load and because cancer cells are less well adapted in an earlier stage of tumour evolution. Thus, adjuvant therapies might not only prolong survival, but might be the key to cure more patients from cancer.

Figure 2.

Phases of cancer progression and therapeutic intervention.