Adding Custirsen to Standard of Care Did Not Improve Survival in MCRPC Patients, AFFINITY Trial Shows

Adding Custirsen to Standard of Care Did Not Improve Survival in MCRPC Patients, AFFINITY Trial Shows

Combining custirsen (OGX-011) with Jevtana (cabazitaxel) and prednisone does not improve survival of metastatic castration-resistant prostate cancer (PC) patients who progressed after prior Taxotere (docetaxel) treatment, new Phase 3 clinical data shows.

The findings were included in the study, “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,” and published in the journal The Lancet Oncology.

The results came from  from the AFFINITY Phase 3 trial (NCT01578655), funded by OncoGenex Pharmaceuticals. The research team was led by Tomasz M. Beer, MD, deputy director and chair for PC research at the OHSU Knight Cancer Institute, in Portland, OR.

Although treatment with Taxotere and prednisone improves survival in metastatic castration-resistant PC, few treatment strategies are available if this first-line therapy fails. Second-line therapy of anti-cancer agent Jevtana with the steroid medicine prednisone is currently used, with favorable data reported in 2010. However, new options are still needed to improve patients’ survival.

Custirsen inhibits the production of clusterin, a stress-induced glycoprotein (a protein with a carbohydrate attached to it) that prevents cell death. Levels of clusterin are increased in some forms of cancer, including PC. Importantly, clusterin has been associated with treatment resistance.

Previous data from the SYNERGY Phase 3 study (NCT01188187) showed that although addition of custirsen to first-line Taxotere failed to improve survival in metastatic castration-resistant PC, benefits could be obtained in patients with poor prognosis.

In the international AFFINITY trial, researchers assessed whether adding custirsen to Jevtana after failure with first-line Taxotere would improve survival in the overall patient group and within subgroups with poor-prognosis.

The study screened a total of 795 men, 635 of whom were enrolled and randomly administered with Jevtana/prednisone (intravenous Jevtana 25 mg/m2 every 21 days, plus oral prednisone 10 mg daily) with or without custirsen (640 mg intravenously on days 1, 8, and 15, plus three previous loading doses). Patients were recruited from 95 cancer centers from eight countries.

The median overall survival was similar between the two groups in the overall group (14.1 months with custirsen vs. 13.4 months with Jevtana and prednisone alone) and among poor-prognosis patients (11 months with custirsen vs 10.9 months with control treatment). Safety information was similar between the two groups.

Of note, the scientists observed that while serum clusterin was decreased, intratumoral custirsen levels were not measured. This assessment would be important for prognosis, because the custirsen dose used in the study may not have been sufficient to induce clinical effect.

The authors suggest that “molecular analysis and stratification of patients based on the molecular features of their tumor may increase the chances of success for future trials of targeted therapy in metastatic castration-resistant prostate cancer”

Overall, the study showed that adding custirsen to Jevtana and prednisone does not improve overall survival among patients with metastatic, castration-resistant PC. Therefore, treatment with Jevtana and prednisone “remains the standard of care for patients with metastatic castration-resistant prostate cancer progressing after docetaxel chemotherapy,” the authors concluded.