Formal discussant of the OlympiA trial, Nadine M. Tung, MD, Director of Breast Medical Oncology and the Cancer Genetics and Prevention Program at Beth Israel Deaconess Medical Center and Harvard Medical School, was enthusiastic about the ability of olaparib to improve invasive disease–free survival and distant disease–free survival in this population of high-risk early breast cancer in BRCA1/2-mutation carriers.

“The take-home message is that the addition of olaparib to standard therapy improved 3-year invasive disease–free survival and distant disease–free survival. This study is practice-changing,” Dr. Tung stated. “There is a reasonable chance that with longer follow-up, survival will be improved.”

“Further, these studies reinforce the need to identify BRCA carriers to make treatment decisions. Less than 50% of women with breast cancer who qualify undergo next-generation sequencing, and the situation is worse for racial minorities,” she continued. “We need to flip the question of which patients need [BRCA] germline testing and redefine which patients don’t need it. We don’t want to miss these cancers.”

Nadine M. Tung, MD

Questions Remain

Despite these promising results, some questions remain, according to Dr. Tung. “Does adjuvant PARP inhibition have the same benefit for all BRCA carriers with breast cancer? Further study is needed in subgroups with prior platinum exposure and hormone receptor–positive/HER2-negative breast cancer, where there appears to be a benefit, but numbers of patients are small and events are few,” she noted. “In addition, does PARP inhibition benefit BRCA carriers with lower-volume disease, such as estrogen receptor (ER)-positive disease with fewer than four involved lymph nodes or CPS + EG score [which incorporates ER status and tumor grade with pretreatment clinical stage and posttreatment pathologic stage] < 3 after neoadjuvant chemotherapy?”

Other questions focus on whether PARP inhibitors can be integrated with other therapies or might allow de-escalation or omission of chemotherapy in lower-risk disease, whether 1 year of olaparib is the optimal duration of treatment, and whether more acute myeloid leukemia and myelodysplastic syndrome will emerge with longer treatment. “Longer follow-up of this trial is important,” she stated. 

“Finally, I think it is time to tackle ‘the last frontier,’ that is, prevention of breast cancer with PARP inhibitors,” she told the audience. 

DISCLOSURE: Dr. Tung has received research funding from AstraZeneca and has received institutional research funding from Myriad Genetics.