Olaparib Improves Outcomes in BRCA-Mutated Metastatic Breast Cancer

The PARP inhibitor olaparib increases progression-free survival and improves quality of life in BRCA-mutated HER2-negative metastatic breast cancer patients.

CHICAGO-Treatment with the PARP inhibitor olaparib increases progression-free survival (PFS) and improves quality of life in BRCA-mutated HER2-negative metastatic breast cancer patients, according to a new study (abstract LBA4) presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6.

“This is the first phase III study to show an advantage of a PARP inhibitor over standard-of-care chemotherapy in breast cancer patients with a BRCA mutation,” said lead author Mark E. Robson, MD, clinic director of the Clinical Genetics Service and medical oncologist at Memorial Sloan Kettering Cancer Center in New York, at a press briefing.

Olaparib was generally well tolerated, with less than 5% of patients discontinuing treatment for toxicity and a lower rate of grade 3 or higher side effects compared with chemotherapy.

“Olaparib could be an effective treatment option for women with BRCA mutations and metastatic HER2-negative breast cancer, including women with triple-negative breast cancer,” said Robson, noting that triple-negative breast cancers that arise in women with inherited germline BRCA mutations are difficult to treat.

Olaparib blocks the cell’s DNA repair machinery. Cancer cells with BRCA mutations are particularly vulnerable to treatments that target PARP. The drug is already approved by the US Food and Drug Administration for use in women with BRCA-related ovarian cancer.

The researchers enrolled 302 patients with inherited BRCA mutations who had metastatic breast cancer that was either hormone receptor–positive or triple-negative (estrogen receptor–negative, progesterone receptor–negative, and HER2-negative). All patients had up to two prior lines of chemotherapy for metastatic breast cancer. Those with hormone receptor–positive cancer had received hormonal therapy.

The patients received either olaparib or standard chemotherapy (either capecitabine, vinorelbine, or eribulin) until progression or the development of severe side effects.

At a median follow-up of 14 months, PFS was 2.8 months longer and the risk for disease progression or death was 42% lower with olaparib monotherapy compared with chemotherapy. The time to second progression was also longer in patients receiving olaparib. Objective response rates were higher with olaparib (60%) than with chemotherapy (29%).

“This study is proof of the principle that breast cancers with defects in a specific DNA damage repair pathway are sensitive to a targeted therapy designed to exploit that defect,” noted Robson.

Severe side effects were less common with olaparib (37%) than chemotherapy (50%). Health-related quality of life was significantly better in the olaparib group.

“Olaparib will probably be best used early in the course of metastatic breast cancer. It helps preserve patient quality of life, offers the chance to postpone the need for IV chemotherapy, and avoids side effects like hair loss and low white blood cell counts,” reported Robson.

ASCO President Daniel F. Hayes, MD, clinical director of the breast oncology program at the University of Michigan Comprehensive Cancer Center, commented, “This represents a major step forward in translational medicine. It is practice-changing. Olaparib has fewer side effects and works better than what we have used in the past.”

Hayes predicted that future trials will combine PARP inhibitors with chemotherapy and that PARP inhibitors would be used earlier in metastatic disease or in the adjuvant setting.