Prostate Cancer Coverage from Every Angle

ESMO 2020: Talazoparib in Men With Metastatic Prostate Cancer and DNA Damage Response Alterations

By: Julia Fiederlein
Posted: Wednesday, October 14, 2020

According to Niven Mehra, MD, PhD, of the Radboud University Medical Center, Nijmegen, the Netherlands, and colleagues, the PARP inhibitor talazoparib appeared to be safe and active in patients with metastatic castration-resistant prostate cancer and DNA damage response alterations. The interim biomarker analysis from the phase II TALAPRO-1 study, which was presented during the European Society for Medical Oncology (ESMO) Virtual Congress 2020 (Abstract 138P), assessed the origins of tumor DNA damage response alterations and potential associations with efficacy.

“Based on this interim analysis, prostate cancers bearing germline DNA damage response alterations may be more sensitive to talazoparib than those bearing only somatic DNA damage response alterations,” the investigators remarked. “Potential reasons include possible gene-specific imbalances in [the] origin of alterations and/or sensitivity to PARP inhibitors and lower tumor subclonality of germline DNA damage response alterations.”

The interim analysis focused on 37 patients with metastatic castration-resistant prostate cancer and DNA damage response alterations likely to sensitize to PARP inhibitors. Patients were required to have received at least one taxane-based chemotherapy and a history of disease progression on at least one novel hormonal therapy. The investigators performed genomic profiling on tumor tissue samples. Saliva samples were collected and sequenced using a custom cancer panel, which included 9 of the 11 genes in the tumor DNA damage response panel.

Patients were categorized by the origin of tumor DNA damage response alterations: 54% had at least one alteration of germline origin; 43% had alterations of somatic origin alone; and 3% were nonassessable for origin. BRCA2 and ATM were among the most common tumor DNA damage response alterations. Patients with alterations of germline origin experienced numerically higher objective response rates than those with alterations of somatic origin alone (35% vs. 6%); however, this result was not significant (P = .053).

Disclosure: For full disclosures of the study authors, visit

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