Doctors just found a way to slow one of the deadliest prostate cancers

Published in Nature Medicine, the Phase III AMPLITUDE trial tested whether adding niraparib, a targeted cancer therapy known as a PARP inhibitor¹, could enhance the effectiveness of the current standard treatment, abiraterone acetate and prednisone (AAP).²

Targeting Genetic Weaknesses in Prostate Cancer

The study focused on men with advanced prostate cancer that had spread to other parts of the body and who were beginning 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 these DNA repair genes malfunction, cancer cells can multiply and spread more rapidly. About one in four men with advanced prostate cancer at this stage have mutations in HRR-related genes, including BRCA1, BRCA2, CHEK2, and PALB2.

How the Study Was Conducted

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

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

The trial was double-blind, meaning neither the patients nor their doctors knew who received the active 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:

• Reduced progression risk: Niraparib lowered the risk of cancer growth by 37% in all participants, and by 48% in those with BRCA1 or BRCA2 mutations.
• Slower symptom worsening: The time until symptoms worsened was about twice as long for those receiving niraparib. Only 16% of these patients experienced significant symptom progression, compared to 34% in the placebo group.
• Potential survival benefit: A trend toward improved overall survival was seen in the niraparib group, though a longer follow-up period is needed to confirm whether it extends life expectancy.

Expert Perspective

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

"These findings are striking because they support widespread genomic testing at diagnosis with use of a targeted treatment for patients who stand to derive the greatest benefit.

"For cancers with a mutation in one of the eligible HRR genes, where niraparib has been approved, a doctor should consider a discussion that balances the risks of side effects against the clear benefit to 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 high blood pressure were reported with niraparib, and 25% of patients required blood transfusions. Treatment-related deaths were also higher in the niraparib group (14 versus 7), though overall discontinuation rates remained low.

The study's authors note that while the results are promising, further research is needed to confirm long-term survival benefits and to 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. In the UK prostate cancer is the most common cancer in men, with more than 56,000 men diagnosed every year, and around 12,000 men die 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 work by blocking the PARP protein, which is involved in repairing damaged DNA in cancer cells. By inhibiting PARP, the cancer cells are unable to repair the DNA damage, leading to their death.
2. Abiraterone acetate and prednisone (APP) are both hormone therapies. This combination blocks androgen production in the testes, adrenal glands, and the tumor itself, slowing cancer growth by reducing the available testosterone for the cancer cells.
3. In the UK, Niraparib is approved to treat some types of cancer but has not yet been approved for prostate cancer. The National Institute for Clinical Excellence has said it waiting for further information, before it can make a decision. https://www.nice.org.uk/guidance/ta1032