Custirsen May Not Improve Survival in Castration-resistant Prostate Cancer

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Custirsen inhibits clusterin production, which is associated with chemotherapy resistance; previous study suggested that custirsen may improve progression-free survival in this setting.
Custirsen inhibits clusterin production, which is associated with chemotherapy resistance; previous study suggested that custirsen may improve progression-free survival in this setting.

Adding custirsen to cabazitaxel and prednisone in the second line does not improve overall survival among unselected patients with metastatic, castration-resistant prostate cancer, according to a study published in The Lancet Oncology.1

There are few treatment options after first-line docetaxel and prednisone for castration-resistant disease. In 2010, cabazitaxel was reported as a favorable second-line therapy, but new options are badly needed. Custirsen inhibits clusterin production, which is associated with chemotherapy resistance; previous study suggested that custirsen may improve progression-free survival in this setting.

For the randomized, open-label, phase 3 AFFINITY trial (ClinicalTrials.gov Identifier: NCT01578655), researchers evaluated whether adding custirsen to cabazitaxel post–docetaxel failure would improve survival in the overall cohort and within poor-prognosis subgroups. Patients were stratified for previous abiraterone/enzalutamide treatment.

Of 795 enrolled patients, 635 were randomly assigned 1:1 to the custirsen (317 patients) group or to the cabazitaxel/prednisone only (318 patients) group. Median overall survival was similar between the 2 groups (14.1 months with custirsen vs 13.4 months with cabazitaxel; hazard ratio [HR], 0.95). Median overall survival was also similar among poor-prognosis patients (11 months with custirsen vs 10.9 months with cabazitaxel; HR, 0.97).

The authors noted, however, that while baseline serum clusterin concentrations are linked to survival, in the AFFINITY trial, intratumoral custirsen levels were not recorded, and it is possible that this is a prognostically relevant measurement.

While safety was similar between the 2 groups, the authors concluded that “[t]o increase the chances of positive findings, the next generation phase 3 trials in castration-resistant prostate cancer should use molecular stratification when feasible.”

Reference

  1. Beer TM, Hotte SJ, Saad F, et al. Custirsen (OGX-011) combined with cabazitaxel and prednisone versus cabazitaxel and prednisone alone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel (AFFINITY): a randomised, open-label, international, phase 3 trial. Lancet Oncol. 2017 Oct 9. doi: 10.1016/S1470-2045(17)30605-8 [Epub ahead of print]

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