The combined use of two new agents that boost the immune system has demonstrated an unprecedented improvement in tumour regression and overall survival for patients with advanced melanoma.
“This is the first trial conducted with this combination in melanoma,” said Mario Sznol of the Yale University School of Medicine, reporting the results of his early-stage study at the American Society of Clinical Oncology meeting. “The combination treatment nearly doubled the median overall survival found in previous studies using either agent alone.”
The two agents, Bristol-Myers Squibb’s marketed Yervoy (ipilimumab) and the investigational treatment nivolumab, are antibodies that belong to a new class of drugs called checkpoint inhibitors. What the antibodies are inhibiting is the tumour cell’s ability to evade attack by the immune system.
With tumour cells, just as with invading microbes, the immune system, with T-cells often leading the charge, is supposed to detect and destroy the physiologic threat. However, once under attack, tumour cells are able to generate ‘retreat’ signals and two of the most common of these are CTLA-4, and PD-1. These commands to retreat can be countermanded by ipilimumab and nivolumab, respectively.
In the study, 94 patients with inoperable stage III or IV melanoma were injected with the combination of checkpoint inhibitors every three weeks.
After two years of follow-up (one year data has been previously reported) the response rate in this patient population (with few other treatment options) was 41%, with nine patients experiencing a complete remission. The same percentage of patients had a greater than 80% reduction in tumour mass.
More importantly, after two years of follow-up the median overall survival rate of the cohort was 79%, at an average time of 39.7 months. “Now, even though this is a small trial,” said Dr Sznol, “This is an impressive two-year overall survival.”
To put the results in context, before ipilimumab, the median survival for these patients was as little as one year, with less than 25% of such patients surviving as long as two years. As put by Jed Wolchok of the Memorial Sloan Kettering Cancer Center, who is one of the key investigators for ipilimumab, “The idea is that we are treating the patient with these drugs – but it’s the patient immune system that’s treating the tumour.”
