After a long period with little progress, a number of new therapies for treating melanoma were highlighted at recent ASCO annual meetings, and this year was no exception. Hoping to build on the successful introduction of the immunotherapy drug Yervoy (ipilimumab), researchers investigated whether it would be effective in treating patients with earlier-stage disease who remained at high risk of recurrence after surgery. Yervoy was approved in 2011 for treating inoperable, late-stage melanoma.
In the phase 3 study, 951 participants whose stage 3 melanoma had been surgically treated were randomized to receive Yervoy or a placebo. After 2.7 years, Yervoy was shown to reduce the risk of recurrence by about 25 percent compared with placebo. However, participants experienced considerable side effects, including inflammation of the colon, thyroid and pituitary gland, as well as skin rash. In fact, more than half (52 percent) of participants discontinued the treatment because of side effect severity, and five treatment-related deaths occurred.
Two other drugs–nivolumab and pembrolizumab–showed success in early phase 1 trials. In a large study of 411 participants with advanced melanoma, pembrolizumab proved effective in participants who had received multiple prior therapies, including Yervoy, as well as those whose metastatic disease was newly diagnosed. Overall, 34 percent of participants experienced tumor response, with an estimated survival rate of 69 percent. Twelve percent of participants experienced treatment-related side effects, but were considered manageable. Pembrolizumab, an antibody that blocks a pathway on T-cells, previously received a breakthrough therapy designation for treating inoperable, late-stage illness, and was granted a priority review under the Food and Drug Administration’s accelerated approval program in May.
In a third study, researchers investigated whether combining the antibody drug nivolumab with Yervoy would improve long-term survival for patients with advanced melanoma. Results showed that 41 percent of the 53 participants responded to the treatment, with 17 percent experiencing complete remissions. The median survival rate was about 40 months, and side effects were considered manageable and reversible.