Johnson & Johnson said a phase 3 study linked apalutamide and hormone therapy around surgery to a lower hazard of recurrence-related events or death in high-risk prostate cancer. The results were presented Oct. 24 at the European Society for Medical Oncology Congress.
The open-label substudy randomized 408 patients with high-risk localized or locally advanced disease. Of those, 102 received apalutamide plus androgen-deprivation therapy (ADT) and surgery, while 306 underwent surgery and could receive local standard care or observation afterward.
Researchers counted biochemical failure, local or regional recurrence, distant metastasis, or death from any cause as events. At a median follow-up of 37.8 months, the event-free survival hazard ratio was 0.38 (95% confidence interval, 0.26-0.55; p<0.0001). Johnson & Johnson characterized this as a 62% reduction in hazard. That measure is not a 62-percentage-point decline in recurrence.
At three years, 63% of patients in the treatment group remained event-free, compared with 41.4% in the surgery group. Median event-free survival was not reached for the treatment group and was 19.1 months for the comparator.
The treatment schedule placed six 28-day cycles on either side of surgery. Patients took apalutamide 240 mg once daily with ADT during those cycles; the operation was radical prostatectomy with pelvic lymph-node dissection.
For distant metastasis or death, the secondary metastasis-free survival analysis reported a hazard ratio of 0.49. An exploratory analysis of time to first subsequent therapy reported a hazard ratio of 0.29. At three years, 64.6% of the treatment group and 32% of the comparator group had not started another therapy.
Grade 3 or higher treatment-emergent adverse events were reported in 31 of 101 patients in the treatment safety group (31%) and 62 of 286 in the comparator safety group (22%). The presentation also listed hot flushes in 64% and urinary incontinence in 63% of the treatment group.
The larger PROTEUS trial compared apalutamide plus ADT with placebo plus ADT, with surgery in both groups. Among 2,109 patients followed for a median of 61.7 months, its hazard ratio for distant metastasis or death was 0.80. Mary-Ellen Taplin, a Dana-Farber Cancer Institute medical oncologist and co-lead investigator, said the substudy findings reinforced the main trial results.
The presentation said follow-up was too short to assess overall survival and that further follow-up is planned. Johnson & Johnson said the regimen is not approved for high-risk localized or locally advanced prostate cancer.
