Analyst Notes: PD-1/PD-L1 checkpoint inhibitors jostling for top position in melanoma

The recent arrival of several immunotherapies, including Yervoy (ipilimumab; Bristol-Myers Squibb), Keytruda (pembrolizumab; Merck & Co.) and Opdivo (nivolumab; Bristol-Myers Squibb), has significantly improved the prognosis for patients with malignant melanoma. These drugs are designed to use patients' own immune systems and have heralded a major revolution in the treatment of melanoma, as well as other tumours. Yervoy, an anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) agent was originally approved in 2011 to treat late-stage melanoma that cannot be removed by surgery. Keytruda and Opdivo are both PD-1/PD-L1 (programmed cell death-1/ligand-1) blocking antibodies that were first approved in September and December 2014, respectively, for patients with advanced or unresectable melanoma.

Insights, Analysis & Opinion

In October 2015, the FDA also approved Yervoy for the treatment of melanoma patients in the adjuvant setting based on the results of the EORTC 18071 study. However, many oncologists are reticent about the use of Yervoy due to the toxicity associated with the drug. Most of the key opinion leaders (KOLs) interviewed by FirstWord for the forthcoming report Malignant Melanoma: KOL Insight agree that the use of Yervoy monotherapy has largely become redundant since the availability of the Opdivo/Yervoy combination regimen, which now is indicated for unresectable or metastatic melanoma patients, regardless of BRAF mutational status. The combination regimen, the first and only FDA-approved combination of immune checkpoint inhibitors, has shown significantly superior progression-free survival compared with Yervoy alone in the CheckMate-067 trial and KOLs expect the use of this regimen to increase in the coming years.

"In my opinion the use of ipi [Yervoy] has dramatically changed because the typical first-line treatment today is anti-PD-1 antibodies [Keytruda, Opdivo]. We have approval for the combination of ipi and nivo [Yervoy+Opdivo] only for a few weeks so what we are currently doing is if a patient is progressing on targeted therapy and has to switch to immunotherapy and is in a good condition we tend to give the combination." - EU Key Opinion Leader

In December 2015, the indication for Keytruda was expanded to include the first-line treatment of patients with unresectable or metastatic melanoma patients regardless of BRAF status. Recent data from the Phase III KEYNOTE-006 study showed patients with unresectable or metastatic melanoma treated with the drug experienced superior overall survival compared with those treated with Yervoy. KOLs acknowledge the clear advantage of anti-PD-1/PD-L1 therapie, but note that further clinical trials of these checkpoint inhibitors in combination with other agents, in melanoma and other cancers, will yet determine the future treatment landscape of the first-line immunotherapy.

For companies operating in the malignant melanoma market in Europe and the US, Malignant Melanoma: KOL Insight is a must read. The report provides actionable insights and commentary on some of the most critical issues in the malignant melanoma market, and provides perspectives on pipeline therapies and how their potential in a rapidly increasing market. The report also discusses how treatment paradigms could change in malignant melanoma. For more information, please click here.

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