Several new anticancer drugs have been approved on the basis of clinical trials that used substandard control arms, and this problematic practice is continuing, noted authors of a recent "Comments and Controversies" article in the Journal of Clinical Oncology.
The PROfound trial is a recent example, said Simon Van Wambeke, MD, of ZNA (Hospital Network Antwerp) Jan Palfijn in Belgium, and colleagues. The trial included patients with metastatic castration-resistant prostate cancer (mCRPC) with a mutation of a predefined set in a DNA repair gene that had progressed on at least one androgen receptor targeting agent (ARTA), enzalutamide or abiraterone. Patients in the experimental arm received a poly (ADP-ribose) polymerase inhibitor, olaparib, and patients in the standard-of-care arm received a physician's choice treatment.
However, the authors said, "the labeling of the control arm as treatment of physician's choice was misleading, because the physician's choice was limited to only abiraterone or enzalutamide, antihormonal treatments that patients had already progressed on before enrollment," the team wrote. "Moreover, almost 20% of patients had already been treated with both of these agents."
Thirty-five percent of patients had not received prior docetaxel, and 45% of docetaxel-pretreated patients had not received prior cabazitaxel -- treatments proven to improve survival in the mCRPC setting.
"Thus, 20% of the patients in the control arm received a treatment that was effectively a placebo with adverse effects (ARTA after progressing on both ARTAs), and 80% were denied an effective taxane chemotherapy," the authors wrote. "For registration trials aiming to establish a new treatment, the new drug should be tested against the best standard of care, and not the minimum treatment that passes as acceptable."