Updated June 9th, 2025

Advanced Prostate Cancer Update: Adding PARP Inhibitor To Standard Of Care Can Notably Improve Outcomes

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PARP Inhibitor Combination Can Help Stop Cancer Progression

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, which evaluated PARP inhibitor niraparib [brand name: Zejula] and abiraterone acetate plus prednisone. Abiraterone acetate is often marketed as Zytiga and prednisone is a steroid medication.
Compared to the 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.

Patients with a type of prostate cancer known as 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.

Metastatic castration-sensitive prostate cancer is a type of cancer where the male hormone testosterone fuels the lesion.

Medical oncologists and researchers Dr. Lucia Nappi and Dr. Kim Chi noted in a report published in ASCO Daily News that “20% to 30% of patients” with advanced prostate cancer (mCRPC) have changes in genes linked to a process called homologous recombination repair (HRR). PARP inhibitors (PARPi) can be a treatment option for these patients. This group’s most common gene mutation is BRCA2, followed by ATM and CDK12 gene mutations.

Genetic testing helps doctors and patients learn specific details, including the molecular or genetic makeup of the prostate cancer in patients. This information can help physicians personalize your battle against cancer. Identifying some mutations could change the way the prostate cancer is treated.

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

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.

“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 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).

Castration-Sensitive Prostate Cancer (mCSPC)

Metastatic castration-sensitive prostate cancer responds to therapies that lower testosterone levels, the male hormone that fuels cancer growth. This type of cancer can also be referred to as hormone-sensitive prostate cancer.

The goal of treatment for this type of cancer is to lower testosterone levels to very low (castrate) levels to slow cancer growth or even shrink tumors.

The backbone of treatment for this diagnosis is usually androgen deprivation therapy (ADT), also known as medical castration. It can be paired with other kinds of therapies depending on factors like where the cancer has spread and how fast it may progress.

Androgen deprivation therapy is given through injections or oral medications. Injection forms are typically given every one to six months. Oral medications are usually taken daily. Doctors can also perform surgery to remove the testicles, a procedure known as “orchiectomy” or castration. However, most doctors will recommend trying medications before considering surgery.

The duration of ADT varies depending on the stage and aggressiveness of prostate cancer. It can go on for a few months to several years — or even a lifetime in some cases.

ADT is effective in slowing down or shrinking prostate cancer tumors, especially in hormone-sensitive cases. However, its effectiveness varies among individuals, and it is often used in combination with other treatments like radiation therapy.

Castration-Resistant Prostate Cancer (mCRPC)

While ADT can be extremely successful at first, some cancer cells may ultimately adapt and become resistant to low testosterone levels. This phase is referred to as castration-resistant prostate cancer. This means that the cancer no longer responds to testosterone-lowering therapies.

Usually, doctors will make this diagnosis when a PSA test comes up elevated despite hormone treatment. But it may also show up on scans or through worsening symptoms.

Treatments may include:

Androgen Deprivation Therapy: This involves a newer class of medications that further suppress androgen (testosterone) signaling, targeting the androgen receptor directly. It is often prescribed when traditional ADT is no longer effective. Side effects may include fatigue, bone density loss, hot flashes, and potential cardiovascular issues. It can provide extended control of the cancer and improved quality of life.
Chemotherapy: Chemotherapy drugs like docetaxel or cabazitaxel are used to target rapidly dividing cancer cells throughout the body. Chemotherapy is typically considered when mCRPC has progressed despite hormonal therapy. Potential side effects include fatigue, nausea, hair loss, and an increased risk of infection. Chemotherapy can help slow cancer progression and alleviate symptoms.
Immunotherapy: Sipuleucel-T is an immunotherapy given by infusion that stimulates the patient’s immune system to target prostate cancer cells. It is considered for patients who have few symptoms of mCRPC but who are not responding to other treatments. Side effects may include fever, chills, and flu-like symptoms. Immunotherapy can extend survival in some patients.
Targeted Therapies: Targeted therapies like abiraterone and enzalutamide focus on specific molecular pathways involved in cancer growth. These medications are often used when mCRPC progresses after hormonal therapy. Side effects may include fatigue, hypertension, and mineral imbalances. Targeted therapies can delay cancer progression and improve quality of life.
Radiopharmaceuticals (Radium-223): Radium-223 is a radioactive drug that targets bone metastases, delivering radiation directly to cancer cells in the bones. It is considered for patients with bone metastases and mCRPC. Side effects may include bone pain, nausea, and an increased risk of fractures.Radium-223 can help manage bone-related symptoms and improve survival.
Pluvicto: A new type of radiation therapy given by injection that targets a molecule called PSMA on the surface of prostate cancer cells has recently been
FDA-approved for mCRPC. Pluvicto is used along with a specialized scan that helps identify the cancer cells that are PSMA-positive. It delivers a high dose of radiation to the PSMA-positive cancer cells, while sparing the normal cells, and can improve survival and quality of life.

Unfortunately, this is a more advanced form of disease and yields a poorer prognosis. This type of prostate cancer often requires aggressive treatments — but research updates, like the ones presented at ASCO this year, are providing a lot of hope and progress.