Lu E, et al. - Researchers describe their experience with PARP inhibitor therapy in patients whose tumors had specific DNA repair gene alterations. These patients were treated at their institution. They noted that PARP inhibitor response was not equally predicted by all DNA repair alterations. All patients showing a response to therapy had tumors with BRCA2 DNA repair alterations, including one without a known pathogenic mutation. Several DNA repair alterations in genes other than BRCA2 were identified among the four nonresponders; these were not clearly pathogenic. There is a need to carefully assess the functional relevance of the DNA repair alterations identified, particularly in genes other than BRCA2, when considering patients for PARP inhibitor treatment.

Methods

• In this retrospective chart review, researchers identified eight patients at Oregon Health & Science University who were treated with PARP inhibition, and determined the effect of the specific DNA repair gene alterations on tumor response and time on treatment with PARP inhibition.

Results

• They identified a number of DNA repair gene alterations.
• Pathogenic BRCA2 mutations were present in three patients and one had a BRCA2 mutation of uncertain significance.
• They noted that alterations in other DNA repair genes was present in the four other patients' tumors, but none of those were clearly pathogenic.
• Findings revealed a statistically significant difference in benefit between patients whose tumors harbored BRCA2 gene alterations and those whose tumors did not, as measured by > 50% decline in prostate-specific antigen levels (100% vs 0%; P=.03) and duration on therapy (31.4 vs 6.4 weeks; P=.03).