Doctors have just found a way to slow down one of the most dangerous types of prostate cancer

Published in Natural medicinethe phase 3 AMPLITUDE trial tested the feasibility of adding niraparib, a targeted cancer treatment known as a PARP inhibitor.¹It can enhance the effectiveness of the current standard treatment, abiraterone acetate and prednisone (AAP).²

Targeting genetic vulnerabilities in prostate cancer

The study focused on men with advanced prostate cancer that had spread to other parts of the body and who were starting treatment for the first time. All participants had mutations in genes involved in homologous recombination repair (HRR), a key system that helps repair damaged DNA.

When DNA repair genes are disrupted, cancer cells can multiply and spread more quickly. About one in four men with advanced prostate cancer at this stage have mutations in genes associated with HRR, including: BRCA1, BRCA2, check2and BALB2.

How was the study conducted?

Currently, the standard treatment for advanced prostate cancer is AAP (or similar drugs). Approximately one in five patients also receive docetaxel chemotherapy. However, patients with HRR gene mutations usually experience more rapid disease progression and shorter survival under standard care.

The AMPLITUDE trial, led by Professor Gerhard Attard from the UCL Cancer Institute, included 696 men in 32 countries, with an average age of 68 years. Half received the combination of niraparib and AAP, while the other half received standard AAP treatment with placebo. More than half of the participants (55.6%) carried mutations BRCA1 or BRCA2.

The trial was double-blind, meaning that neither patients nor their doctors knew who received the effective treatment.

Key findings from the AMPLITUDE trial

After a median follow-up period of just over two and a half years (30.8 months), researchers found notable benefits from the drug combination:

• Reduce the risk of progression: Niraparib reduced the risk of cancer growth by 37% in all participants, and by 48% in those with BRCA1 or BRCA2 mutations.
• Symptoms worsen more slowly: The time it took for symptoms to worsen was about twice as long for those receiving niraparib. Only 16% of these patients saw significant improvement in symptoms, compared to 34% in the placebo group.
• Potential survival benefit: A trend toward improved overall survival was observed in the niraparib group, although a longer follow-up period is needed to confirm whether this increases life expectancy.

Experts’ point of view

Professor Attard said: “Although current standard treatments are very effective for the majority of patients with advanced prostate cancer, a small but very large proportion of patients have limited benefit. We now know that prostate cancers with alterations in HRR genes represent a large group of patients whose disease recurs rapidly and has an aggressive course. By combining with niraparib we can Delaying the recurrence of cancer and hopefully significantly extending life expectancy.

“These results are striking because they support broad genomic testing at diagnosis with targeted therapy for the patients who will receive the greatest benefit.

“For cancers with a mutation in one of the qualifying HRR genes, where niraparib is approved, the physician should consider discussing a balance between the risk of side effects and the clear benefit of delaying disease growth and worsening symptoms.” ³

Side effects and safety

While the treatment was generally well tolerated, side effects were more common in the niraparib group. Significantly more cases of anemia and hypertension were reported with niraparib, and 25% of patients required blood transfusions. Treatment-related deaths were also higher in the niraparib group (14 versus 7), although overall discontinuation rates remained low.

The study authors note that although the results are promising, more research is needed to confirm the long-term survival benefits and explore the impact of newer imaging techniques and broader genetic testing.

Prostate cancer: key statistics

Globally, an estimated 1.5 million men are diagnosed with prostate cancer each year. Prostate cancer is the most common cancer in men in the UK, with more than 56,000 men diagnosed each year, and around 12,000 men dying from the disease each year.

The AMPLITUDE trial was sponsored by Janssen Research & Development, part of Johnson & Johnson.

Notes

1. PARP inhibitors, such as niraparib, are a type of targeted therapy that works by blocking the protein PARP, which is involved in repairing damaged DNA in cancer cells. By inhibiting PARP, cancer cells are unable to repair DNA damage, leading to their death.
2. Abiraterone acetate and prednisone (APP) are both hormonal treatments. This combination inhibits androgen production in the testicles, adrenal glands, and the tumor itself, slowing cancer growth by reducing the testosterone available to cancer cells.
3. In the United Kingdom, Niraparib is approved to treat some types of cancer but is not yet approved to treat prostate cancer. The National Institute for Clinical Excellence said it was waiting for more information before it could make a decision. https://www.nice.org.uk/guidance/ta1032