AFFINITY

AFFINITY randomised 635 men whose metastatic castration-resistant prostate cancer had progressed after docetaxel to cabazitaxel and prednisone with or without custirsen, stratified by opioid use for cancer-related pain, radiographic evidence of progression on first-line docetaxel, and previous abiraterone or enzalutamide.

Median follow-up was 28.3 months in the custirsen group and 29.8 months in the control group. Median overall survival was 14.1 months (95 percent confidence interval 12.7 to 15.9) with custirsen and 13.4 months (12.1 to 14.9) without, hazard ratio 0.95 (0.80 to 1.12, log-rank p=0.53). In the prespecified poor-prognosis subgroup, the co-primary endpoint, it was 11.0 months (9.3 to 13.3) against 10.9 months (8.2 to 12.4), hazard ratio 0.97 (0.80 to 1.21, p=0.80).

The commonest grade 3 or worse adverse events with custirsen against control were neutropenia (70 of 315 against 61 of 312), anaemia (68 against 49), fatigue (23 against 18), asthenia (16 against 8), bone pain (16 against 5) and febrile neutropenia (16 against 9). Serious adverse events occurred in 155 (49 percent) against 132 (42 percent). Twenty-seven men died within 30 days of treatment in the custirsen group against 17 in the control group.

With SYNERGY, this ended the clusterin hypothesis as a therapeutic target in prostate cancer.