The results of the Phase II TOPARP-A trial, published today in the New England Journal of Medicine, indicate that the PARP inhibitor olaparib is able to halt tumor growth in men with treatment-resistant advanced prostate cancer. The trial has been described as a ‘milestone in cancer treatment’ and presents the first evidence for the benefits of precision medicine in prostate cancer.
TOPARP-A was carried out by an international consortium of researchers, led by a team from The Institute of Cancer Research in London (UK). The study participants included 49 men with treatment-resistant advanced prostate cancer, all of whom received treatment with olaparib.
Analysis indicates that 33% of the men included in the trial (n = 16) responded to the therapy, as defined by an established set of clinical criteria. In those who responded to the treatment, olaparib halted prostate cancer growth, produced enduring decreases in PSA levels, reduced circulating tumor cell counts in the blood, and produced radiological responses on CT scans and MRI.
The study also incorporated next-generation sequencing analysis of tumor samples, which indicated that up to 30% of these men had tumors with DNA repair defects. Specifically, 16 individuals were noted to have tumors deficient in DNA repair mechanisms, of which 14 responded very well to olaparib – accounting for the majority of those who benefited from the treatment.
“Our trial marks a significant step forward in the treatment of prostate cancer, showing that olaparib is highly effective at treating men with DNA repair defects in their tumors. It also proves the principle that we can detect prostate cancers with specific targetable mutations using genomic sequencing to deliver more precise cancer care by matching treatment to those men most likely to benefit,” commented Johann de Bono, chief investigator of The Institute of Cancer Research. “I hope it won’t be long before we are using olaparib in the clinic to treat prostate cancer, or before genomic stratification of cancers becomes a standard in this and other cancers.”
Further work will now be carried out in the form of the TOPARP-B trial, which will only include individuals with disease that has detectable DNA repair mutations.