Bone-Targeted Therapy in Prostate Cancer in 2017: Lost Opportunities, Confusion, and Controversy
Mené sur 1 245 patients atteints d'un cancer de la prostate de stade métastatique ou localement avancé, cet essai randomisé évalue l'intérêt, du point de vue de l'amélioration de la survie globale à long terme, et la toxicité de l'ajout du célocoxib, un anti-inflammatoire non stéroïdien, à une hormonothérapie anti-androgénique (durée médiane de suivi : 69 mois)
Since 2004, the number of management options for patients with metastatic prostate cancer has increased dramatically, with six agents showing improvements in overall survival (OS). In 2002, zoledronic acid (ZA) demonstrated efficacy in reducing the risk of skeletal-related events (SREs) as well as in delaying their appearance.1 Until then, no agent had shown any improvement in survival in metastatic castration-resistant prostate cancer (mCRPC), but this underpowered study did show an unexpected trend in improving OS. Around the same time, the Medical Research Council from the United Kingdom (MRC-PR05) reported results from the use of oral clodronate. Initially, the investigators reported no survival advantage in hormone-sensitive metastatic prostate cancer, but with longer follow-up, the study did show an improvement in OS. Of note, clodronate was continued from the hormone-sensitive state and throughout the castration-resistant prostate cancer (CRPC) state.2,3 Given the positive results with ZA in the latest stage of the disease, it made sense to investigate whether it would be even more effective in an earlier disease state, such as in metastatic hormone-sensitive prostate cancer. Also of interest was whether it would add to the effectiveness of docetaxel, which had been the first agent to demonstrate a survival advantage in men with mCRPC. The Cancer and Leukemia Group B/National Cancer Institute of Canada conducted a randomized study in newly diagnosed metastatic prostate cancer that compared administering ZA upfront at the time of initiating androgen deprivation therapy versus starting it at the first sign of CRPC (defined as a rising prostate-specific antigen [PSA]).4 Not surprisingly, there was a low rate of SREs in those patients, who were still hormone sensitive and at an early stage of the CRPC state. The study was discontinued early given the low event rate and the inability to delay the first appearance of CRPC. Given that this was an SRE event–driven study, no attempt was made to capture long-term survival data.