PD-1s show early promise in melanoma brain metastases


One of the most frequent and terminal complications of advanced melanoma—the most aggressive form of skin cancer—is brain metastases. Melanoma brain metastases (MBM) occur in approximately 40–50% of Stage IV melanoma patients. MBM is a major cause of treatment failure, and is linked to poor prognosis and significant morbidity. However, it has been appreciably under-investigated. Despite being an admittedly ominous diagnosis, MBM is not necessarily a death sentence. A couple of recent clinical trials, brought to the spotlight here, underline that conclusion. 

The use of systemic therapies could provide much needed solutions in MBM; fortunately, clinical trials investigating such therapies have started demonstrating noteworthy results. In particular, immune checkpoint inhibitors that target programmed cell death protein 1 (PD-1) are emerging as potential therapeutic strategies in MBM.

Immune checkpoint inhibitors that target programmed cell death protein 1 (PD-1) are emerging as potential therapeutic strategies in MBM

Bristol-Myers Squibb’s (BMS's) PD-1 immunotherapy wonder drug, Opdivo (nivolumab), has cemented its position as physicians’ first choice in many countries in the first-line setting of unresectable or metastatic melanoma, either alone or in combination with BMS’s other immune-based treatment, Yervoy (ipilimumab). However, Opdivo has not yet demonstrated survival benefits in an MBM patient cohort. To address this, an ongoing Phase II clinical trial named CheckMate 204 evaluated the safety and efficacy of Opdivo + Yervoy followed by Opdivo monotherapy in patients with MBM. In an update of the CheckMate 204 trial at the 2016 Society for Melanoma Research Congress, BMS revealed that the safety profile of Opdivo + Yervoy was similar to that of previously documented melanoma patients without MBM, with no elevated neurologic adverse events.

Another startlingly successful immuno-oncology agent, Merck and Co.’s PD-1 Keytruda (pembrolizumab), has also been established as a go-to treatment option in first-line advanced melanoma. Similarly to Opdivo, Keytruda is being investigated in patients with MBM. In an ongoing Phase II study, Keytruda has had notable responses in patients with MBM, demonstrating the potential role that systemic therapy could have for this complication.

There is light on the treatment horizon for patients with MBM, and that light is shed by compelling data from clinical trials involving PD-1s. The number of MBM trials that involve immunotherapies is steadily rising. These trials might be favourable signs marking the potential for more therapeutic options for MBM to be developed, which could, in turn, offer renewed hope for this patient population.