Abstract
Background
Prior to the approval of the anti-CTLA-4 antibody ipilimumab in 2011, patients suffering from melanoma with distant metastases faced a poor prognosis with a median overall survival of 6–10 months. The approval of immune check point inhibitors, which can achieve long-term survival for patients with metastatic melanoma, represents a breakthrough.
Aim and methods
The currently approved systemic therapies for melanoma, taking into account the data presented at the Annual Meeting 2017 of the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO), are summarized in this review.
Results and discussion
Compared to ipilimumab, the two anti-PD-1 antibodies pembrolizumab and nivolumab are showing higher efficacy with lower toxicity. The combination of nivolumab and ipilimumab was approved in 2016 and achieved a response rate of 58% and a 3-year survival rate of 58%. Severe grade 3/4 adverse events occurred in 55% of the patients. The early diagnosis of immune-mediated side effects and their adequate treatment, using systemic glucocorticosteroids and other immunosuppressive drugs if necessary, is an indispensable prerequisite for successful therapy. Combined nivolumab and ipilimumab achieved intracranial response rates of 42–55% in patients with metastatic melanoma and brain metastases, with no increase in toxicity compared to patients without brain metastases. In light of the therapeutic success of immune checkpoint inhibitors, several studies are currently underway to evaluate anti-PD-1 antibodies in the adjuvant setting. Current and future studies are increasingly investigating innovative immunocombination therapies, e. g. anti-PD-1 antibodies in combination with IDO inhibitors (IDO, indoleamine-pyrrole 2,3-dioxygenase). Data available now suggest high efficacy and low toxicity.
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