Several new anticancer medications have been approved based on clinical trials that used subpar control arms. According to the authors of a recent "Comments and Controversies" paper in the Journal of Clinical Oncology, this problematic practice is still going on.
According to Simon Van Wambeke, MD, of ZNA (Hospital Network Antwerp), Jan Palfijn in Belgium, and colleagues, the PROfound trial is a recent example. Men with metastatic castration-resistant prostate cancer (mCRPC) who already had progressed on at least one second-line androgen receptor-targeted drug, enzalutamide or abiraterone, were eligible for the trial. Men in the experimental arm were given olaparib, a parp inhibitor; men in the control arm were given a physician's choice medication.
"The labeling of the control arm as treatment of physician's choice was misleading," the authors concluded, "since the physician's option was limited to just abiraterone or enzalutamide, antihormonal medicines that patients had previously advanced on before enrollment." "Moreover, over 20% of patients had previously been treated with both of these agents." We know that prior exposure to either of these treatments means that the other will not be as effective.
Thirty-five percent of men had not previously received docetaxel, and 45 percent of docetaxel-pretreated patients had not previously received cabazitaxel – therapies that have been shown to increase survival in the mCRPC.
As a result, 20% of men in the control arm received a medication that was virtually a placebo with adverse effects (a second-line hormone treatment after failing one or both). The scientists wrote that eighty percent (80%) were denied effective taxane chemotherapy. "For registration trials aimed to establish a new treatment, the new drug should be tested against the best standard of care, not the minimum treatment that passes as acceptable."
Failure to respond to this concern will undermine our confidence in the FDA-approved treatments that are on the market. In addition, it will be harmful because we will be offering substandard treatments at a tremendous economic cost and the possibility of increasing personal side effect profiles.
