Olaparib is an oral PARP inhibitor that exhibits antitumor activity by blocking the cellular single-strand DNA repairing machinery. It is approved for the treatment of recurrent ovarian cancer patients with germline BRCA mutation. Olaparib has potential in treating other BRCA-mutated cancer patients who also have defect in DNA repair. In a phase III trial (OlympiAD), olaparib monotherapy was compared with chemotherapy in HER2-negative metastatic breast cancer patients with germline BRCA1 or BRCA2 mutations. 205 patients were assigned to receive olaparib monotherapy (300 mg twice daily) and 97 were assigned to receive standard therapy with single-agent chemotherapy (capecitabine, eribulin, or vinorelbine in 21-day cycles). Progression-free survival was 2.8 months longer in the olaparib group than in the chemotherapy group (7.0 months versus 4.2 months; hazard ratio 0.58). The objective response rates were higher with olaparib (60%) than with chemotherapy (29%). Olaparib was also generally well tolerated. The adverse events of grade 3 or higher were 36.6% in the olaparib group and 50.5% in the chemotherapy group. These results reveal that olaparib increases progression-free survival (PFS) and improves living qualities of HER2–negative breast cancer patients with germline BRCA mutation.
Robson M, Im SA, Senkus E, et al., N Engl J Med. 2017 Jun 4.