Niraparib/Abiraterone Acetate Combo Maintains Baseline HR-QOL in HRRM+ mHSPC

Health-related quality of life (HR-QOL) remained at baseline for patients with metastatic hormone-sensitive prostate cancer (mHSPC) with homologous recombination repair mutations (HRRm) receiving niraparib (Akeega) and abiraterone acetate with prednisone, according to patient-reported outcomes (PROs) from the AMPLITUDE trial (NCT04497844) revealed that were shared at the 2025 ESMO Congress.

With 696 patients randomized 1:1 to either the niraparib arm or a placebo arm, at least 94.3% of patients completed an online questionnaire, which was given to patients at screening, during cycles 1 to 25, and then every 4 months up to end of treatment. The questionnaire used FACT-P, EQ-5D-5L, and BPI-SF to measure HR-QOL.

What were the PROs for patients in the AMPLITUDE trial?

Between 76% and 85% of patients in the niraparib arm reported via the GP5: Side Effects Bother single question that they were “not at all” or “a little bit” bothered by adverse effects (AEs) vs between 86% and 93% in the placebo arm.

FACT-G scores were not significantly different across arms; the overall mean LS change from baseline was 0.02 for the niraparib arm (SE, 0.50) and 0.77 for the placebo arm (SE, 0.50) of 0.50 points (P = .289). The mean baseline FACT-G score for the niraparib arm was 79.7 (SD, 14.9) compared with 79.3 (SD, 15.2) in the placebo arm.

These scores fluctuated slightly, with the niraparib arm’s FACT-G score decreasing between cycles 2 to 4, and the placebo arm’s score increasing at that time, which lead study author Dana Rathkopf, MD, a genitourinary medical oncologist at Memorial Sloan Kettering Cancer Center in New York, New York, expanded on during her presentation of the data.

“You can see that there was an initial reduction in the HR-QOL score in the niraparib arm, which may have been explained by the onset of the most frequently observed adverse events, which included hypertension and anemia, which were subsequently well-managed,” said Rathkopf. “The score returned to baseline from cycles 5 and onward.”

Rathkopf also noted that the niraparib arm’s FACT-G scores declined toward the end of the trial.

“There was a slight separation of the curves toward the end for the niraparib arm,” said Rathkopf. “This may have been because there was a higher number of niraparib patients in the last cycles on study.”

The trend that FACT-G scores followed was echoed across most PROs measured.

HR-QOL FACT-P scores remained comparable across arms overall after following a similar pattern as FACT-G scores in the first 4 cycles. The mean baseline FACT-P score for the experimental arm was 113.3 (SD, 20.2) and 112.7 (SD, 20.4) in the placebo arm. The overall LS mean change from baseline in FACT-P scores was -0.05 (SE, 0.67) in the niraparib arm vs 1.22 (SE, 0.67) in the placebo arm (P = 0.181).

Scores on the FACT-P physical well-being subscale followed the same trend, with the scores varying in the first 4 cycles but remaining similar overall. The mean baseline scores here were 23.5 (SD, 4.6) in the niraparib arm and 23.6 (SD, 4.4) in the placebo arm. The overall LS mean change from baseline was -0.43 (SE, 0.15) in the experimental arm compared with -0.01 (SE, 0.15;) in the placebo arm (P = .0467).

EQ-5D-5L Visual Analog Scale scores varied slightly from the pattern observed in the other PROs measured.

“In the first cycle, there was a slight decline in both the placebo and niraparib arms, which returned to baseline for the placebo and returned after cycle 4 to baseline for the niraparib arm,” explained Rathkopf.

The mean baseline EQ-RD-5L score for patients in the niraparib arm was 74.9 (SD, 17.4) and 73.9 (SD, 18.6) in the placebo arm. The overall LS mean change from baseline was 1.82 (SE, 0.63) and 2.59 (SE, 0.63), respectively (P = .390).

Additionally, time to progression as measured by BPI-SF worse pain intensity scores was similar between arms (HR 0.95; 95% CI 0.72-1.26; P = 0.7).

What is the clinical significance of the AMPLITUDE trial?

AMPLITUDE, a randomized, double-blind, placebo-controlled phase 3 trial, investigated niraparib plus abiraterone acetate and prednisone vs placebo plus abiraterone acetate and prednisone in patients with HRR-mutant mHSPC. Both arms also received androgen deprivation therapy (ADT).

The study met its primary end point of radiographic progression-free survival (rPFS) and found that the niraparib combination significantly reduced the risk of rPFS by 37% (HR, 0.63; P = .0001) and reduced time to symptomatic progression by 50% (HR< 0.50; P < .0001). The trial found the combination’s safety profile to be consistent with previous findings.

With a clinical data cutoff of January 7, 2025, the median follow-up was 30.8 months, with a median of 25 cycles in both arms.

The current standard of care for this patient population is ADT plus an androgen receptor inhibitor with or without docetaxel.

Reference

Rathkopf D, Agarwal N, Graff JN, et al. Patient (pt) reported outcomes (PROs) from AMPLITUDE, a randomized placebo-controlled phase III trial of niraparib (NIRA) and abiraterone acetate (AA) plus prednisone (P) in metastatic hormone-sensitive prostate cancer (mHSPC) with homologous recombination repair mutations (HRRm). Presented at: ESMO 2025 Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA91.