AMPLITUDE: HRQOL is maintained with niraparib plus abiraterone

Patient-reported outcomes (PROs) from the phase 3 AMPLITUDE trial (NCT04497844) evaluating niraparib plus abiraterone acetate (Zytiga) plus prednisone indicate that baseline health-related quality of life is maintained in metastatic hormone-sensitive prostate cancer (mHSPC) with homologous recombination repair (HRR) mutations.¹

Dana E. Rathkopf, MD, a genitourinary medical oncologist at Memorial Sloan Kettering Cancer Center in New York, New York, reported the data during a presentation at the 2025 European Society for Medical Oncology Congress in Berlin, Germany.

The randomized, double-blind, placebo-controlled AMPLITUDE trial included patients with mHSPC, an alteration in at least 1 HRR-eligible gene, and ECOG performance status of 0-2. Patients were excluded if they had previously received any PARP inhibitor or androgen receptor pathway inhibitor other than abiraterone plus prednisone. Prior allowed treatments for mHSPC included androgen deprivation therapy for 6 months or less, docetaxel for 6 cycles or less, abiraterone plus prednisone for 45 days or less, and palliative radiotherapy. Patients were stratified according to BRCA2 vs CDK12 vs all other alterations, prior docetaxel (yes or now), and disease volume (high vs low).

A total of 696 patients were randomly assigned 1:1 to receive niraparib 200 mg once daily plus abiraterone 1000 mg once daily plus prednisone 5 mg once daily plus ADT (348 patients) or to placebo plus abiraterone 1000 mg once daily plus prednisone 5 mg once daily plus ADT (348 patients). The clinical data cut-off was January 7, 2025. Median follow-up was 30.8 months, and median number of treatment cycles was 25 for both arms.

As reported earlier this year in Nature Medicine, niraparib plus abiraterone plus prednisone met its primary end point of radiographic progression-free survival. Treatment with the combination was associated with a 37% reduced risk of radiographic progression or death (HR, 0.63, P = .0001), as well as a 50% reduction in time to symptomatic progression (HR, 0.50, P < .0001).² The safety profile of the combination was found to be consistent with previously reported data.³

Participants completed PRO e-questionnaires at screening, cycles 1 to 25, and then every 4 months until the end of treatment. The investigators reported an overall questionnaire completion compliance rate of at least 94.3%. Instruments utilized included FACT-G, FACT-G item GP5 (“I am bothered by side effects of treatment”), FACT-P, FACT-P physical well-being subscale, and the EQ-5D-5L visual analogue scale.

The mean baseline FACT-G total score for the niraparib group was 79.7 (standard deviation [SD], 14.9) and was 79.3 (SD, 15.2) for the placebo group. An initial reduction in the health-related quality of life score was observed in the niraparib group, “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, and the score returned to baseline from cycle 5 and onward,” Rathkopf said.

The overall least squares mean change from baseline for FACT-G total score was 0.02 for the niraparib group vs 0.77 for the placebo group (P = .289).

Mean baseline total FACT-P score was 113.3 (SD, 20.2) in the nirarparib group vs 112.7 in the placebo group, and overall least squares mean change from baseline was –0.05 (SE, 0.67) for the niraparib group vs 1.22 (SE, 0.67) for the placebo group (P = .181). Similar to the FACT-G scores, the scores between the arms were comparable following a decline in the niraparib group during the first 4 cycles. A similar trend was observed for the FACT-P physical well-being subscale and the EQ-5D-5L visual analog scale. For the latter, Rathkopf said, “In the first cycle, there was a slight decline in both the placebo and the niraparib arm, which returned to baseline for the placebo and then returned after cycle 4 to baseline for the niraparib arm.”

For the FACT-P physical well-being subscale, mean baseline score was 23.5 (SD, 4.6) for the niraparib group vs 23.6 (SD, 4.4) for the placebo group. The overall least squares mean change from baseline was –0.05 (SE, 0.15) for the niraparib group vs –0.01 (SE, 0.15) for the placebo group.

For the GP5 side effects bother question, 76% to 85% of patients in the niraparib group answered “not at all” or “a little bit” bothered compared with 86% to 93% of patients in the placebo group.

“The baseline health-related quality of life was maintained following an initial but not significant reduction with niraparib plus abiraterone and prednisone. The initial reduction in the health-related quality of life may be explained by the common AEs observed during initial cycles, which can be managed with dose modifications and supportive care. The key takeaway from this abstract is that the addition of niraparib to abiraterone plus prednisone maintained baseline health-related of life while providing clinical benefit in HRR-mutated patients, with a safety profile consistent with that previously observed for this combination,” Rathkopf said in her concluding remarks.

DISCLOSURES: Rathkopf noted disclosures with Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb/Celgene, Curium, Genentech, Janssen, Myovant Sciences, Novartis, Promontory Therapeutics, Pfizer, Genentech/Roche, and Janssen Oncology.

REFERENCES

1. Rathkopf DE, 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: European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. LBA91. https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.esmo/static/esmo2025_abstracts/LBA91.html.pdf

2. Attard G, Agarwal N, Graff JN, et al. Niraparib and abiraterone acetate plus prednisone for HRR-deficient metastatic castration-sensitive prostate cancer: a randomized phase 3 trial. Nat Med. 2025. doi:10.1038/s41591-025-03961-8

3. Chi KN, Rathkopf D, Smith MR, et al. Niraparib and abiraterone acetate for metastatic castration-resistant prostate cancer. J Clin Oncol. 2023;41(18):3339-3351. doi:10.1200/JCO.22.01649