Patients with advanced melanoma, who have been treated with the monoclonal antibody, Ipilimumab ( Yervoy ), can survive for up to ten years, according to the largest analysis of overall survival for these patients.
Ipilimumab is a human monoclonal antibody that activates the immune system to fight melanoma skin cancer by targeting a protein receptor called Cytotoxic T-Lymphocyte Antigen 4 ( CTLA-4 ). In melanoma, CTLA-4 is inhibited from recognising and destroying cancer cells, but Ipilimumab turns off the inhibitory mechanism, enabling CTLA-4 to continue killing the cancer cells.
It is already known that some patients treated with the drug survive for long periods, with one phase III clinical trial showing an overall survival rate of 18% after five years. Therefore, researchers collected data on 1861 patients in 12 prospective and retrospective studies to provide a more precise estimate of Ipilimumab’s effect on long-term survival.
In addition, they analysed data from a further 2985 patients who had been treated with the drug but were not part of any clinical trial, giving the researchers data on a total of 4846 patients.
The analysis of the 1861 patients has shown that the median overall survival was 11.4 months. Among these patients, 254 patients ( 22% ) were still alive after three years. There were no deaths among patients who survived beyond seven years, at which time the overall survival rate was 17%.
The longest overall survival follow-up in the database is 9.9 years.
The plateau, which started at three years and continued through to ten years, was observed regardless of dose ( 3 or 10 mg/kg ), whether the patients had received previous treatment or not, and whether or not they had been kept on a maintenance dose of the drug. However, as this was not a randomised comparison, one cannot draw direct conclusions on differences between the doses or the populations.
When data from the total 4846 patients were analysed, the median overall survival was 9.5 months, with a plateau in overall survival starting around three years for 21% of the patients. This slightly lower survival rate was because there were limited and incomplete data on overall survival, and patients given Ipilimumab through the extended access programme tended to be more ill and with more advanced disease.
The limitation of this study is that it is a pooled analysis from phase II, phase III and observational data and not from a single randomised, controlled study. However, these results are consistent with the findings from randomised clinical trials and confirm the durability of the plateau in overall survival, previously shown to extend to at least five years but now shown to extend up to ten years. ( Xagena )
Source: European Cancer Congress ( ECC ), 2013