PARP Inhibitor Combination Can Help Slow Cancer Progression

  • Patients with metastatic castration-sensitive prostate cancer (mCSPC), who have specific genetic mutations, were found to have improved survival by using the PARP inhibitor niraparib [Zejula] combined with standard therapy with an androgen receptor (AR) pathway inhibitor.
  • The findings came from the phase III AMPLITUDE trial, which evaluated niraparib and abiraterone acetate [Zytiga] plus prednisone.
  • Compared to a placebo group, the combination of niraparib plus abiraterone acetate with prednisone (AAP) lessened the risk of cancer progression or death by 37% for mCSPC patients with gene mutations in the homologous recombination repair (HRR) pathway, like BRCA 1/2.

Patients with metastatic castration-sensitive prostate cancer (mCSPC) who have specific genetic mutations were found to have improved survival by using a targeted treatment called PARP inhibitors combined with standard therapy with an androgen receptor (AR)-pathway inhibitor.

The findings came from a phase III trial called AMPLITUDE, and the results were presented at the 2025 American Society of Clinical Oncology (ASCO) annual meeting. The trial evaluated PARP inhibitor niraparib [brand name: Zejula] and abiraterone acetate [Zytiga] plus prednisone.

The trial compared niraparib plus abiraterone acetate with prednisone (AAP) to a placebo plus AAP, and ultimately found that niraparib lessened the risk of cancer progression or death by 37% for mCSPC patients with gene mutations in the homologous recombination repair (HRR) pathway.

The approach could provide a much-needed solution for about one-third of mCSPC patients who harbor HRR pathway mutations, like BRCA 1/2, as this patient population often fairs worse when treated with the standard AR-pathway inhibitor.

Finding The Best Combination

“We really do have a lot of new options for our patients to keep them not just alive longer but healthier longer,” Dr. Stephen Freedland, a urologist at Cedar Sinai Medical Center in Los Angeles, tells SurvivorNet Connect of the exciting updates presented at this year’s ASCO conference.

“The question really becomes for us in the research community, ‘What’s the best combination? How can we be even more aggressive with bad disease early?’ And hope would be that we could take some of these patients where the tumor’s already spread and actually cure their cancer. So really intense treatment for a year or two, and then actually stop all treatment and allow the patient to live the normal life, normal quality of life.

“And so that’s where the field is trying to go, but it’s not so easy. These trials take time. We need a lot of patience,” he adds.

The phase III AMPLITUDE trial was designed to determine whether PARP inhibitors work in people with castration-sensitive prostate cancer.

To obtain these findings, a total of 696 patients with mCSPC and HRR gene alterations were randomly assigned to receive either niraparib plus AAP (348 patients) or placebo plus AAP (348 patients).