Apalutamide plus ADT improves PFS2 in mCSPC

The addition of apalutamide, a novel androgen receptor inhibitor, to androgen deprivation therapy (ADT) reduced the risk of progression while on first subsequent therapy or death (PFS2) in men with metastatic castration-sensitive prostate cancer (mCSPC), according to exploratory analysis of the phase III TITAN* trial.

“Apalutamide plus ADT reduced the risk of second progression or death, regardless of novel hormonal therapy or taxane chemotherapy as a first subsequent life-prolonging therapy,” said study author Professor Neeraj Agarwal from the Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, US, who presented the results at ASCO GU 2020.

Study participants were 1,052 men with mCSPC and at least one bone metastasis, and ECOG performance status 0–1. Previous treatment with docetaxel and ADT** were allowed. The patients were randomized 1:1 to receive ADT plus either apalutamide (240 mg/day) or placebo.

Previously published results showed a 33 percent reduction in the risk of death with apalutamide vs placebo at 24 months (overall survival [OS], 82.4 percent vs 73.5 percent; hazard ratio [HR], 0.67, 95 percent confidence interval [CI], 0.51–0.89; p=0.0053). Apalutamide also fared better than placebo in terms of radiographic progression-free survival (24-month rPFS, 68.2 percent vs 47.5 percent; HR, 0.48, 95 percent CI, 0.39–0.60; p<0.001). [N Engl J Med 2019;381:13-24]

Eighty-seven and 190 patients assigned to apalutamide and placebo, respectively, received first subsequent systemic therapy. Of these, 27.6 and 32.6 percent of apalutamide and placebo recipients, respectively, received novel hormonal therapy (enzalutamide or abiraterone acetate), while 34.5 and 36.3 percent, respectively, received taxane chemotherapy. Apalutamide and placebo recipients who received hormonal therapy were treated for a median 11.9 and 11.1 months, respectively, while those who received taxane chemotherapy were treated for a median 11.0 and 11.3 months, respectively.  

Second progression-free survival (PFS2) was greater among apalutamide vs placebo recipients (median not reached in both groups; HR, 0.66, 95 percent CI, 0.50–0.87; p=0.0026). [ASCO GU 2020, abstract 82]

This risk reduction was consistent regardless of whether patients were receiving hormonal therapy (HR, 0.684, 95 percent CI, 0.482–0.971; p=0.0326) or taxanes (HR, 0.634, 95 percent CI, 0.456–0.881; p=0.0062).

Agarwal acknowledged limitations of the study including the non-randomized selection of subsequent therapy and small number of events while on subsequent therapy, which “preclude determination of best subsequent therapy based on these data.”

“[Nonetheless,] PFS2 benefit is an indicator of effective early intensification of the treatment, is consistent with OS benefit we have seen with this agent, and together shows totality of treatment trajectory. These results may assist with counselling of patients with mCSPC who are contemplating various treatment options,” he concluded.