By Matthew Owens
Prostate cancer is the second most common cancer for males and the fifth most common overall. Prevalence rates are shown in the figure below. Although genes and environmental factors can confer differential risk for individuals, in general 1 in 8 men will develop prostate cancer in their lifetime. In a forthcoming article in The Lancet Oncology, a large multi-national randomised controlled trial showed that a new combination drug treatment has no effect on survival rates for men with castration-resistant metastatic prostate cancer. Furthermore the addition of the trial drug proved to be highly toxic. The study was conducted over 187 sites in 31 countries including South America and Chile.
Data Source: Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM GLOBOCAN 2008 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer, 2010. Available from: http://globocan.iarc.fr. Note: incidence is likely correlated with presence of screening programmes in different regions.
Patients (1224) were given standard first-line chemotherapy treatment of docetaxel (interferes with cell division) plus prednisone(suppresses androgens that stimulate cancer growth). In addition, participants in the trial were randomised to receive the aflibercept (inhibiting new blood vessel growth) or placebo. At follow up, an average of 35 months later, 873 men had died overall (71%) but the survival time was essentially equivalent in both groups (21.2 months in the treatment group and 22.1 for those taking placebo).
So called phase 3 trials are large scale randomised treatments that usually only come about after smaller scale clinical and pre-clinical evidence has amassed, increasing the likelihood of efficacy. The report highlights a number of previous research studies examining the effect of docetaxel and prednisone which have recruited thousand of men and cost an estimated US$1 billion. The current trial was based on limited evidence and an expectation that agents such as aflibercept would become effective.
Lead author Professor Ian Tannock from the Princess Magaret Cancer Centre, Toronto said, “I think there is a need for more preclinical data showing benefit for the experimental strategy, need for early (phase 2) [trials] indicating a substantial signal of benefit to move to phase 3. The bar should be set higher (by FDA, EMA) for improvements in outcome with agents that we know will add toxicity – thereby allowing smaller trials to detect them and earlier stopping for futility.”
Given the multi-centre nature of the study, it is plausible that there are effects of treatment in some geographical regions, or genetic population but not in others. However, Tannock said, “until we have done a more thorough analysis I cannot comment on regional differences in outcome or toxicity, but from a brief glance any such trends were not significant.”
The study was funded by Sanofi and Regeneron Pharmaceuticals Inc.