Continuing enzalutamide after progression improves PFS in mCRPC

In patients with metastatic castration-resistant prostate cancer (mCRPC) who experience disease progression while on enzalutamide treatment, continuing enzalutamide appears to improve progression-free survival (PFS), according to results of the phase IIIb PRESIDE trial.

“[E]nzalutamide plus docetaxel and prednisolone demonstrated a statistically significant reduction in the risk of progression compared with placebo plus docetaxel and prednisolone,” said study author Professor Axel Merseburger from the University Hospital Schleswig-Holstein – Campus Lübeck in Lübeck, Germany, at ASCO GU 2022.

Chemotherapy-naïve patients with mCRPC and ECOG performance score 0–2 who had progressive disease while on open-label enzalutamide only (160 mg/day; study period 1) were randomized, double-blind, to receive docetaxel (75 mg/m² Q3W) and prednisolone (10 mg/day) plus either enzalutamide (160 mg/day; n=136) or placebo (n=135) until disease progression (study period 2).

The median age of patients was 71.5 and 69.0 years in the enzalutamide and placebo groups, respectively, and a majority were White (97.8 and 99.3 percent, respectively). Baseline prostate specific antigen (PSA) levels were higher in the enzalutamide than placebo group (median 36.9 and 28.1 μg/L, respectively) and 36.8 and 47.4 percent, respectively, had both bone and soft tissue metastases.

There was a significant 28 percent reduction in the risk of progression in the enzalutamide compared with the placebo group (median 9.53 vs 8.28 months; hazard ratio [HR], 0.72, 95 percent confidence interval [CI], 0.53–0.96; p=0.027). [ASCO GU 2022, abstract 15]

The results appeared consistent across the subgroups analysed including ECOG performance score, age, and baseline PSA levels. Notably, the benefits appeared greater in patients with tissue or bone and tissue metastases (HRs, 0.42 and 0.63, respectively) or visceral disease (HR, 0.29), though the number of events in these subgroups was small.

“[These findings suggest] that those aggressive tumours may benefit from this therapy intensification in mCRPC,” noted Merseburger.

Time to PSA progression was also significantly improved with enzalutamide compared with placebo (median 8.44 vs 6.24 months; HR, 0.58, 95 percent CI, 0.41–0.82; p=0.002).

Mean PSA level reduction from period 2 baseline was greater in the enzalutamide than placebo group at 13 weeks (-37.12 percent vs 9.11 percent).

Overall response rate was numerically higher in the enzalutamide than placebo group (31.6 percent vs 25.9 percent; p=0.142), with complete response rates of 19.1 percent vs 12.6 percent and partial response rates of 12.5 percent vs 13.3 percent.

Treatment-emergent adverse events (TEAEs) were documented in 97.8 and 97.0 percent of enzalutamide and placebo recipients, respectively, and serious TEAEs in 49.3 and 38.5 percent, respectively. TEAEs led to permanent discontinuation of study drug in 8.8 percent and 6.7 percent, respectively. There were 13 and seven deaths in the respective groups (9.6 percent vs 5.2 percent), two and one, respectively, deemed related to docetaxel.

The most common (≥15 percent) TEAEs in the enzalutamide group were asthenia (34.6 percent), neutropenia (33.8 percent), and alopecia (32.4 percent), while the most common in the placebo group were neutropenia (33.3 percent), diarrhoea (32.6 percent), and alopecia (27.4 percent).

“We hypothesized that continued administration of enzalutamide will maintain control of responsive tumour lesions and enable docetaxel to target clonal subpopulations that adopted accessory pathways to enhance survival and proliferation,” said Merseburger.

“These data suggest that continued treatment with enzalutamide plus docetaxel offers clinical benefit and could be a future treatment option for some patients who progress on enzalutamide alone,” he said.