Talazoparib Shows Clinical Benefit In PALB2-Mutated HER2-Negative Metastatic Breast Cancer Patients


Talazoparib has been approved by the US FDA for treatment of HER2-negative breast cancer patients with germline BRCA mutation. However, whether patients with other homologous recombination repair (HRR) gene mutations can benefit from talazoparib remains unclear. In the phase 2 TBB study, 20 patients with at least one non-BRCA HRR gene mutation have been enrolled (13 HER2-negative breast cancer; 3 pancreatic cancer; and 4 other cancer types) and received talazoparib monotherapy. The ORR was 31% (4/13) and the CBR (CR+PR+SD ³ 6 months) was 54% (7/13) in the breast cancer population. Interestingly, within the four responders, three had germline PALB2 mutation and the remaining one had CHEK2/FANCA/PTEN mutations. These results suggest that talazoparib may offer the therapeutic opportunity for HER2-negative breast cancer patients who have a non-BRCA HRR mutation, especially for those with a PALB2 mutation.

J Clin Oncol 37, 2019 (suppl; abstr 3006)