Niraparib Combination Substantially Extends Progression-Free Survival in Advanced Prostate Cancer
LONDON - A new combination therapy of niraparib, abiraterone acetate, and prednisone demonstrated a statistically significant and clinically meaningful improvement in median second progression-free survival (rPFS) for men with metastatic castration-sensitive prostate cancer (mCSPC) harboring alterations in homologous recombination repair (HRR) genes, according to results published today in Nature Medicine. The phase 3 trial offers a potential new treatment option for a patient population with limited therapeutic choices.
The study, involving 696 patients, revealed a median rPFS not reached in the niraparib arm compared to 44.0 months in the placebo arm (HR, 0.66; 95% CI, 0.51-0.86; P* = .002).This benefit was observed across the entire intent-to-treat (ITT) population, with 348 patients receiving niraparib plus abiraterone acetate/prednisone and 348 receiving placebo plus the same hormonal therapy. Subgroup analyses showed promise in both the BRCA mutation subgroup (191 patients) and the broader HRR effector subgroup (230 patients).
Researchers also found improvements in objective response rate and time to prostate-specific antigen (PSA) progression with the addition of niraparib. The objective response rate was 72% versus 74% in the niraparib and placebo arms, respectively, with a longer duration of response observed in the niraparib arm (HR, 0.55; 95% CI, 0.35-0.86; *P = .008).Time to PSA progression was also significantly improved (HR, 0.50; 95% CI, 0.39-0.65; P* < .0001).
the trial did reveal a higher incidence of adverse events (AEs) with the niraparib combination. Any grade AEs occurred in 99.7% of the niraparib arm versus 98.0% of the placebo arm, with grade 3/4 toxicities affecting 75.2% and 58.9% of patients, respectively. Serious aes were reported in 39.2% and 27.6% of patients, and 14.7% versus 10.3% discontinued treatment due to AEs. Deaths attributed to AEs occurred in 4.0% and 2.0% of patients in the niraparib and placebo arms, respectively.
Common toxicities of any grade included anemia (51.6% vs 23.9%), hypertension (43.8% vs 32.5%), constipation (35.2% vs 16.4%), nausea (30.8% vs 14.4%), and fatigue (26.2% vs 18.4%). Grade 3 or higher AEs included anemia (29.1% vs 4.6%), hypertension (26.5% vs 18.4%), and hypokalemia (11.5% vs 10.9%).
“for cancers with a mutation in 1 of the eligible *HRR genes, where niraparib has been approved, a doctor should consider a discussion that balances the risks of [AEs] against the clear benefit to delaying disease growth and worsening symptoms,” stated Dr. Johann de Bono (Attard) in a press release from UCL News.
The study population had a median age of 68 years (range,40-88) and was predominantly White (70.7% vs 73.9% in the niraparib and placebo arms, respectively) and from Europe (48.3% vs 50.9%). Most patients in both arms had an ECOG performance status of 0 (69.5% vs 62.6%), a Gleason score greater than 7 at diagnosis (79.3% vs 75.3%), and metastatic disease (86.5% vs 86.8%).
References
- 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.
