Evaluating olaparib for metastatic breast cancer with BRCA1/2 and other gene mutations.

This study was carried out to examine the effectiveness of olaparib (Lynparza) for the treatment of metastatic breast cancer (MBC; cancer that has spread) with gene mutations (abnormalities). The authors found that this treatment was effective for patients with MBC with BRCA1/2 mutations.

Breast cancer (BC) is one of the most common cancers found in women. BRCA1 and BRCA2 gene mutations are can be found in many patients with BC. BRCA1 or BRCA2 mutated BC is often found in young patients and can be very resistant to current treatment options.

Olaparib is a PARP (proteins involved in DNA repair) inhibitor. BRCA1 and BRCA2 mutated cancers have been shown to be responsive to PARP-inhibitors. However, the response rate to olaparib of patients with MBC with BRCA1/2 and other genetic mutations has not been determined. 

There were 54 patients with MBC enrolled in this trial. 87.5% of these patients had mutations in BRCA1/2 or other less common genes. Participants received olaparib 300 mg-tablets daily. There were two groups in this study. Group 1 included patients with mutations in other genes than BRCA1/2. Group 2 included patients with BRCA1/2 genes. Patients were followed for an average of 4.2 months.

The overall response rate (ORR) in group 1 was 33%. In group 1, all responses were recorded in patients with a gPALB2 mutation. In patients with a gPALB2 mutation, the ORR was 82%, and the clinical benefit rate (CBR; the percentage of patients who have tumor shrinkage or whose disease does not progress with treatment). In these patients, the average length of time without cancer progression was 13.3 months.

The ORR in group 2 was 31%. Patients with the BRCA1/2 mutation had an ORR of 50% and a CBR of 66%. The average time without cancer progression in these patients was 6.3 months.

Most side effects of olaparib treatment were mild to moderate and included nausea (9%), anemia (26%), and hair loss (4%).

The authors concluded that olaparib is effective in the treatment of MBC in patients with BRCA1/2 and other mutations. The authors suggest that these results show the importance of genetic analysis of BC. 

The study lacked large numbers of patients with gene mutations that are less common than BRCA1/2 mutations. This study was funded by AstraZeneca, the manufacturer of olaparib.