For rare patients with indolent stage IV melanoma, curative resection remains an option, he said. And young patients with good performance status may want to try high-dose interleukin-2, which leads to cure in about 5% of cases: "But it’s toxic [and] expensive, and we have failed to provide good predictive factors for this, so we really struggle with knowing who and when to treat" with IL-2.
Biochemotherapy – the combination of IL-2 and interferon with chemotherapy – has some benefit in patients with rapidly progressive melanoma and high LDH levels.
Although adoptive T-cell therapy can produce dramatic remissions in some patients, it has not proved very practical because of factors such as labor intensiveness. "It's great science, but it's not really adding to the benefit of the vast majority of patients," Dr. O'Day said.
Ipilimumab expands on these options, with short-term therapy offering the possibility of long-term disease control for about a third of patients. Ongoing trials will continue to provide data on the investigational agents that target MAP kinase signaling.
Additionally, combining new drugs from different classes has tremendous potential for improving melanoma outcomes, he noted. "The obvious next step is to combine – in BRAF-mutated cases – a BRAF drug that is breaking tumors up [90% of the time or more] with an immune drug that can then come in and, with the tumor exposed and the antigens released from necrosis and apoptosis, it makes sense that there should be great synergy there," he said.
Moreover, this could be done on an outpatient basis, in contrast to existing combination therapies, which have required inpatient stays because of toxicity and route of admission, he noted. "So it's a major step forward."
Dr. O'Day reported receiving research support from and being a consultant to Bristol-Myers Squibb, GlaxoSmithKline, and Roche, and being on the speakers bureau for Bristol-Myers Squibb