DNA repair mechanism damage targeted in advanced disease

CHICAGO — Patients diagnosed with metastatic castration-resistant prostate cancer whose tumors harbor genes with DNA damage repair alterations appear to maintain progression free survival when treated with the poly (ADT)-ribose polymerase (PARP) inhibitor olaparib (Lynparza), researchers reported here.

In a trial in which patients were enrolled on the basis of their having DNA damage repair genetic alterations, researcher said they were able to observe that patients with BRCA 1 or BRCA 2 alterations could achieve progression free survive for a median of 8 months.

At the 55th annual meeting of the American Society of Clinical Oncology, Joaquin Mateo, MD, of Vall d’Hebron Hospital, who performed the study while a fellow at Royal Marsden Hospital in London, said that a third of the patients with the BRCA 1 and BRCA 2 gene alternation had achieved progression free survival of more than a year.

Among 30 men with confirmed mutations in their BRCA 1/2 genes, 25 patients or 83.3% of that group responded to treatment with olaparib and 4 of 7 patients with PALB2 alterations or 57.1% of that small group of patients responded to the treatment, he said in his oral presentation. He also said more modest activity was seen for men whose tumors included ATM alterations and CDK12 alterations.

In commenting on the study, David Graham, MD, associate professor of medicine at Levine Cancer Center at Atrium Health, Charlotte, North Carolina, said, “There have been studies that indicate that these types of DNA repair alterations can be present in as many as 30% of men with metastatic prostate cancer. We consider it standard of care that any man with metastatic prostate cancer should have a genetic consultation. We would like to get genetic tests in these patients.”

“Olaparib has antitumor activity against metastatic castration-resistant prostate cancer with DNA damage repair gene alterations,” Mateo said. “Gene aberration type matters as response rates and progression free survival rates differ between gene subgroups.”



The study received support from AstraZeneca.

Mateo disclosed relevant relationships with AstraZeneca, Janssen, Roche, Astellas Pharma, Sanofi, Ipsen, and BelGene.

Graham disclosed relevant relationships with Biopep Solution.


Mateo J, et al “TOPARP-B: A phase II randomized trial of the poly(ADP)-ribose polymerase (PARP) inhibitor olaparib for metastatic castration resistant prostate cancers with DNA damage repair alterations” ASCO 2019.


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