Background: 90% of all skin tumour related deaths are caused by malignant melanoma. Nivolumab is an anti-PD1 checkpoint inhibitor used in patients with advanced malignant melanoma and as adjuvant therapy for patients with high-risk metastatic melanoma. The aim of this work is to evaluate the real world evidence of Nivolumab for the treatment of malignant melanoma in a systematic review and to contrast the results with the evidence from pivotal RCTs.

Method: A systematic literature search was carried out. As a result, ten publications with 1,425 patients from 614 references were included and evaluated in the systematic review. All of them were exclusively uncontrolled observational studies. In a further step, the real-world evidence was compared with the evidence of the pivotal studies, differentiated according to therapy lines, in order to assess whether and to what extent the results of the RCTs are also reflected in real clinical application. However, no study for adjuvant use in the real clinical setting could be identified and included.

Results: As a result of the comparison, there was good concordance between the outcomes of the included real-world studies and those of the pivotal RCTs across various lines of therapy, with slightly lower response rates. However, it becomes apparent that first-line treatment with Nivolumab, both monotherapy and in combination with Ipilimumab, is associated with a better outcome, and that when given in second- or follow-up-line treatment, outcomes may depend on the type of prior therapy and on other prognostic factors such as the BRAF mutation status.

Conclusion: Observational studies under everyday medical conditions are a valuable complement to RCTs for the assessment of therapies. However, due to older and sicker patients, the clinical outcomes are somewhat worse than in the pivotal trials.