Feb 23, 2015
By Shira Klapper, Senior Writer/Editor
A meta-analysis of the immunotherapy ipilimumab for the treatment of advanced melanoma adds to the evidence showing that the drug confers sustained, long-term survival benefits. The study, published in the Journal of Clinical Oncology (JCO) online, ahead of print, February 9, found that 22% of patients with advanced melanoma who receive ipilimumab are alive at three years after treatment. One of the central findings of the study was that among these 22% of patients, the survival curve reaches a plateau at year three, meaning that few patients who reach the three-year milestone will die after that, but will instead go on to live for five to 10 years post-treatment.
According to first author, Dirk Schadendorf, MD, the study, “Pooled Analysis of Long-Term Survival Data from Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma,” is “The first meta-analysis looking at Ipilimumab. It is also the largest analysis of melanoma patients ever conducted, with close to 5000 patients all treated with one treatment. The strength of this analysis is that the studies were carried out over many years, enabling follow-up data to be gathered up to 10 years after treatment.”
Ipilimumab has dramatically changed the treatment landscape of malignant melanoma over the past several years. The drug, which works by blocking cytotoxic T-lymphocyte antigen-4 (CTLA-4), a molecule that puts the “brakes” on T cells, has brought unprecedented survival rates to patients with late-stage metastatic melanoma; previous studies have shown that 23% of patients who received the drug have lived for five years or longer. By comparison, in the age of chemotherapy, fewer than 10% of patients with melanoma reached the five-year mark.
An analysis of 12 pooled studies
The meta-analysis focused primarily on the overall survival (OS) of 1,861 patients pooled from 12 different studies examining the survival benefits of Ipilimumab. The12 studies included seven clinical trials sponsored by Bristol-Myers Squibb (BMS) (two phase III and five phase II trials), three phase I/II trials sponsored by the National Cancer Institute (NCI), and two observational studies sponsored by BMS.
Despite some differences between the 12 studies, the majority of the 1,861 patients received the approved dose of 3 mg/kg or the investigational dose of 10 mg/kg. Likewise, two-thirds of the 1,861 patients had previously been treated for advanced disease prior to receiving ipilimumab; for the remaining third of patients, ipilimumab was their first treatment. Among all patients, ipilimumab was given at least every three weeks for up to four doses.
In terms of follow-up, eight out of the 12 studies had more than a five-year minimum follow-up time. Patients in the NCI-sponsored studies were followed for more than 10 years and 10% of all patients were followed for at least 50 months, with a maximum follow up of 119 months.
The meta-analysis also included a secondary focus on data from 2,985 patients in an expanded access program (EAP). EAPs make investigational new drugs available, in special cases, to patients with serious disease who are not eligible for controlled clinical trials.
Analysis shows a survival plateau
Among the 1,861 patients in the primary analysis, the median OS was 11.4 months.
The study also showed that 22% of patients were alive at year three after treatment, amounting to 254 patients (For those patients who received ipilimumab treatment as their first treatment, 26% were alive at year three; among patients who were previously treated with another drug, 20% were alive at year three). It was among these 254 patients that the survival plateau of three years was observed. The median follow-up time for these patients was 69 months and the longest follow-up was 10 years.
An analysis of patients from the EAP showed a similar 3-year survival rate of 21% and the same survival plateau, extending up to 10 years.
Commenting on these findings, Dr. Schadendorf said, “One has to keep in mind that ipilimumab is only given four times over an interval of three to 12 weeks and then these patients are free of treatment for the rest of their lives, more or less, if they are the 22% of patients benefitting from ipilimumab. This is very unique for oncologic treatment, and for these 22% this is good news.”
Dirk Schadendorf, MD is the Director of the Department of Dermatology at the University of Duisburg-Essen, in Germany. He has been an ASCO member since 2005.
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Schadendorf D, Hodi S, Robert C. Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J Clin Oncol. Epub 2015 Feb 9.
The Exclusive Coverage series on ASCO.org highlights selected research from JCO and JOP with additional perspective provided by the lead or corresponding author.
@ 2014 American Society of Clinical Oncology