The Rapid Emergence of Novel Therapeutics in Advanced Malignant Melanoma

Abstract

For decades, no cancer therapy had been shown to improve average survival in metastatic melanoma. Two critical events have occurred, the discovery of melanoma driver mutation subsets and the discovery of immune checkpoint inhibitors, which have allowed for the development of modern, effective therapies. These findings have facilitated a rapid emergence of novel therapeutics for the disease with multiple FDA approvals in the last several years. The drugs vemurafenib, trametinib, and dabrafenib, which inhibit the commonly mutated BRAF pathway, have been approved based on improvements in survival outcomes. Agents that block immune checkpoints on lymphocytes allowing for immune cell activity against melanoma have also been approved based on improved survival outcomes such as ipilimumab and nivolumab. Pembrolizumab, another immune checkpoint inhibitor, has also been approved based on the response rate and duration of response in a phase 1 trial. Further agents and combinations of approved agents are positioned to possibly further increase this tally of approved drugs. This review will discuss recently approved novel agents and select drugs in development in advanced melanoma.

Concealed complete response in melanoma patients under therapy with immune checkpoint inhibitors: two case reports

“…Checkpoint inhibitors are effective in the treatment of metastatic melanoma, with approval of the first antibodies in the U.S. in 2011 [ 1 ]. Ipilimumab, the anti-CTLA4 antibody, demonstrated an increased overall survival [ 2 ].…”

Radiological imaging in all stage III melanoma: current practice in the U.K.

“…1 The outcome of patients with late-stage disease has improved considerably with the development of targeted therapy and immunotherapy agents including vemurafenib, dabrafenib, ipilimumab, nivolumab and pembrolizumab. [2][3][4] This improvement is expected to continue over the coming years. Novel immunotherapy agents may have better outcomes in patients with low-volume asymptomatic disease, making early detection of metastases important.…”

“…It has been observed that treating the basic inflammatory condition improved insulin sensitivity and subsequently the glycaemic control. [3][4][5] Nevertheless, the nature of glycaemic control in diabetic patients with concomitant psoriasis has been given little attention to date.…”

Development and validation of the patient roles and responsibilities scale in cancer patients

“…More patients with cancer are living longer due in part to advances in molecular biology and the development of novel-targeted therapies [ 1 ]. There is growing recognition that assessment of the quality of this extended survival is important, namely how broader aspects of patients’ lives are managed and affected.…”