New Emerging Treatments
Despite these advances, the median survival in the first-line setting of mCRPC is approximately 20 months, and in the postdocetaxel setting is about 15 months. The modest benefits conferred to these recently approved agents, means new tolerable drugs are necessary to make future gains. Promising new therapies include hormonal agents, as well as other immunotherapeutics and antiprostate-specific membrane antigen therapies are in advanced stages of clinical development.
Some of these trials incorporating molecular analyses are ongoing better understand tumor biology, and to identify and evaluate new biomarkers. Nowadays, OS is the only accepted end point for regulatory purposes in Phase III trials. To compensate, several ongoing Phase III trials have incorporated biomarkers as circulating tumor cells (CTCs) into their trial design in order to prospectively evaluate CTCs as surrogate of response and survival. Isolation of CTCs based on epithelial surface markers and quantification using the Cell Search platform was cleared through the FDA in 2008. This was based in a study which demonstrated that patients with a CTC count >5 detected in 7.5 ml blood had a significantly lower OS compared to patients with CTC <5.
There are concerns that ongoing Phase III trials may be contaminated if patients go off study treatment to start one of the newly approved agents or take the agent subsequently. These realities make clinical trial design more challenging than ever. We have summarized the most promising and encouraging new drugs in Phase III studies below.
TAK-700 is a reversible CYP17 inhibitor with preferential inhibition of 17,20-lyase over 17-hydroxylase activity. This selective inhibition may in theory reduce the need for corticosteroid supplementation. However, early data suggest that TAK-700 has similar response profiles as abiraterone and steroid support is needed to avoid tocixicity. The most common adverse events were fatigue, nausea and constipation. Two randomized Phase III studies of TAK-700 and prednisone versus placebo and prednisone are underway that include patients with chemotherapy-naive and docetaxel-refractory mCRPC, respectively (ClinicalTrials.gov identifiers: NCT01193244 and NCT01193257). However, to date, we have no data from either of these Phase III trials by which to judge its efficacy. Recently, the Southwest Oncology Group has initiated a new, randomized, double-blind, multicenter, Phase III trial designed to compare androgen deprivation therapy (ADT) + bicalutamide (Casodex) to ADT + the investigational drug TAK-700 in men newly diagnosed with metastatic, hormone-sensitive prostate cancer (ClinicalTrials.gov identifier: NCT01809691).