J Clin Oncol: salvage radiotherapy + enzalutamide for high-risk prostate cancer with PSA recurrence after radical surgery

Enzalutamide is an androgen receptor signaling inhibitor that directly targets androgen receptors (AR) and plays a role in the three steps of the AR signaling pathway: inhibiting androgen binding, preventing nuclear shift, and weakening DNA binding; In turn, it inhibits the growth of cancer cells and promotes apoptosis
of cancer cells.

The aim of this study was to explore whether enzalutamide combined with salvage radiotherapy (SRT) prolongs survival without prostate-specific antigen (PSA) progression (FFPP)
in patients with recurrent prostate cancer after radical prostatectomy (RP).

This is a randomized, double-blind, placebo-controlled, multicenter Phase 2 clinical trial of patients with biochemical recurrence of prostate cancer after RP who are randomized to SRT plus enzalutamide (160 mg, 1/day) or placebo (1:1) for 6 months
.
Stratification
was performed according to central, surgical resection marginal state (R0 vs R1), PSA (PSA≥0.
5 vs <0.
5 ng/mL), and pathological Gleason sum (7 vs 8-10).
The primary endpoint is FFPP.

Secondary endpoints were time to local recurrence, metastasis-free survival, and safety
within the radiotherapy area.

Testosterone levels varied in both groups

A total of 86 patients were randomized into two groups, with a median follow-up of 34 months
.
The median PSA level before SRT was 0.
3 (range: 0.
06-4.
6) ng/mL, with 56 (65%) patients with extrastate lesions (pT3), 39 (45%) patients with Gleason suming 8 to 10 points, and 43 (50%) patients with a positive surgical resection margin (R1).

FFPP rates in different subgroups of patients in both groups

Compared with the placebo group, the FFPP of enzalutamide group was significantly improved (hazard ratio [HR] 0.
42, p=0.
031), and the two-year FFPP rates were 84% and 66%,
respectively.
Subgroup analysis showed that patients with pT3 versus pT2 and R0 versus R1 benefited significantly from enzalutamide (HR: pT3 vs pT2=0.
22 vs 1.
54 [p=0.
019]; R0 vs R1=0.
14 vs 1.
00[p=0.
023]）
。

There were not enough secondary endpoint events for analysis
.
The most common adverse events were grade 1 to 2 fatigue (enzalutamide versus placebo: 65% versus 53%) and frequent urination (40% versus 49%)
.

In summary, for high-risk prostate cancer patients with PSA recurrence after RP, SRT combined with enzalutamide monotherapy is safe for 6 months, and compared with SRT alone, it can also delay the progression
of PSA in the test patients.

Original source:

Phuoc T.
Tran, et al.
Phase II Randomized Study of Salvage Radiation Therapy Plus Enzalutamide or Placebo for High-Risk Prostate-Specific Antigen Recurrent Prostate Cancer After Radical Prostatectomy: The SALV-ENZA Trial.
J Clin Oncol.
November, 2022.
https://ascopubs.
org/doi/abs/10.
1200/JCO.
22.
01662?role=tab