ICR study finds Lynparza effective for advanced prostate cancer

Researchers at the Institute of Cancer Research (ICR) have announced a breakthrough in treating advanced prostate cancer using an existing drug. The study, published in the Journal of Clinical Investigation, suggests that the drug Lynparza (olaparib) could benefit a broader range of patients.

Prostate cancer claims around 12,000 lives annually in the UK. In its advanced stages, the disease spreads to nearby tissues or organs and other parts of the body. Previous research has indicated that approximately 30% of men with advanced prostate cancer have tumors with DNA repair defects. Some of these tumors respond well to PARP inhibitors, including Lynparza, which is marketed by AstraZeneca and Merck & Co, known as MSD outside the US and Canada.

The research received funding from several organizations, including AstraZeneca, Prostate Cancer UK, Cancer Research UK, the Medical Research Council, Movember, and the Prostate Cancer Foundation. The team analyzed biopsies from 124 patients with advanced prostate cancer. They discovered that the RNASEH2B gene, crucial for DNA repair, was commonly lost in 44% of patients. In these cases, at least half of their cancer cells exhibited this genetic loss, and 20% of patients showed RNASEH2B loss in 75% of their cancer cells.

RNASEH2B loss means that the gene does not function correctly, impacting the cell's ability to repair DNA damage. This defect could potentially be targeted by existing drugs like Lynparza. To further understand this, researchers examined biopsy samples from patients without BRCA1 and BRCA2 mutations, which are tumor suppressor genes. These patients had participated in the TOPARP-A and TOPARP-B clinical trials, led by the ICR’s Clinical Trials and Statistics Unit.

The findings were significant. In 13 out of 18 patients, the number of cells with RNASEH2B loss decreased following treatment with PARP inhibitors. Additionally, six patients experienced a reduction in circulating tumor cells, with three patients enjoying relapse-free survival periods ranging from eight to 22 months. This suggests that Lynparza could be effective in a more extensive patient population with RNASEH2B genetic aberrations.

In summary, this study opens up new possibilities for treating advanced prostate cancer. By targeting the RNASEH2B genetic defect, existing drugs like Lynparza could offer new hope to patients who previously had limited treatment options. Further clinical trials are needed to confirm these results and potentially extend the benefits to a larger group of patients.

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