Karim Fizazi, MD, PhD, of the Gustave Roussy Institute, Villejuif, France, talks about the final results from the AFFINITY Phase III trial, which investigates the use of custirsen together with chemotherapy for second-line metastatic prostate cancer that has been resistant to not only hormonal therapy but also first-line chemotherapy (NCT01578655). He explains that the goal of combining chemotherapy and custirsen, is to achieve a better job than chemotherapy alone. The AFFINITY trial was a randomized study where patients with very advanced disease who had failed hormonal therapy and chemotherapy were treated with either cabazitaxel plus prednisone plus custirsen or cabazitaxel and prednisone alone. Patients continued treatment until cancer progression and the primary end point was survival.
The results of the trial showed that there was no superiority of custirsen when added to chemotherapy. Therefore, what happened to serum clusterin was looked at to see if clusterin was not a good enough target or because the drug was not good enough to target clusterin. In the control arm there was little effect whether clusterin was lowered or not by chemotherapy. In the experimental arm, those patients who achieved a mild decline in clusterin while on custirsen do much better than those who do not achieve vast effect.
He explains that in conclusion, the addition of custirsen to second-line chemotherapy with cabazitaxel did not significantly improve overall survival (OS). There was no new safety signal and no imbalance of active drugs beyond progression. So there are two possible questions - either clusterin is not a relevant target in this disease, or the target was not inhibited enough with the compound we have at the moment. Furthermore, in order to achieve a successful next-generation trial, the population must be selected based on biomarker.
Recorded at the 2016 annual meeting of the European Society of Medical Oncology (ESMO), held in Copenhagen, Denmark.