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Adjuvant Olaparib a Win for High-Risk, BRCA-Mutant Early Breast Cancer

Elias Obeid, MD, MPH

 

Adding one year of the PARP inhibitor olaparib to standard adjuvant therapy significantly extended invasive disease-free survival and distant disease-free survival in women with high-risk, HER2-negative, BRCA-mutant early breast cancer, according to results of the phase-3 OlympiA trial. The results apply to both those with hormone-receptor-positive and those with triple negative breast cancer.

PARP inhibitors work by blocking the PARP family of proteins that help repair damaged DNA.  namely BRCA1 and BRCA2. BRCA1 and BRCA2 mutations lead to faulty DNA repair, making BRCA-deficient tumor cells more sensitive to PARP inhibitors. 

Olaparib is already approved for patients with metastatic HER2-negative breast cancer having a germline BRCA1/2 mutation. Researchers at Fox Chase were part of the team of international researchers responsible for enrolling patients into the OlympiA trials.  

“This is the first time that giving an adjuvant PARP inhibitor showed a benefit for the outcomes of patients with triple-negative breast cancer or hormone-receptor-positive breast cancer,” said Elias Obeid, MD, MPH, interim chief, Division of Breast Medical Oncology and assistant professor, Department of Clinical Genetics. “Although data from longer follow-up duration of this trial are needed, the current results are promising in terms of improved survival. Additionally, those results are compelling and potentially open the door for PARP inhibitors to be tested as a choice in the prevention setting for BRCA1/2-mutation carriers.”

In the double-blind trial, researchers enrolled 1,836 patients at 420 centers across 23 countries. Eligible patients were those with HER2-negative, early breast cancer with BRCA1 or BRCA2 germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned to one year of oral olaparib 300 mg or placebo twice daily.

Interim analysis study results showed that olaparib improved the three-year invasive disease-free survival by 42% and the three-year disease-free survival by 43% compared with placebo. Olaparib had an acceptable safety profile with no excess serious adverse events. 

The results of the study were presented at the 2021 ASCO Annual Meeting and published in The New England Journal of Medicine.

According to Obeid, Fox Chase follows the National Clinical Cancer Network (NCCN) guidelines for genetic testing in women diagnosed with breast cancer but admitted that the results of this study will likely open the door for more women with breast cancer to undergo genetic testing to screen for BRCA1 and BRCA2, given the implications this study may have on treatment of women with high-risk early stage HER2-negative breast cancer. 

Olaparib is not yet FDA approved for high-risk, HER2-negative, BRCA-mutant early breast cancer; however, earlier this year, the American Society of Clinical Oncology (ASCO) updated its clinical guideline to recommend one year of adjuvant treatment with olaparib for this patient population.

According to Melissa M. McShane, MD, assistant professor, Department of Hematology/Oncology,  next steps for olaparib in early breast cancer will include studies of patient populations not included in the OlympiA trial, such as those with intermediate- or low-risk disease. 

“Patients with high-risk disease did so well with this drug,” McShane said. “Next, we may also want to look at whether one year of adjuvant olaparib allows us to de-escalate chemotherapy for these patients.”

Things to know about olaparib:

  • Olaparib is a PARP inhibitor, which is a drug that blocks the PARP family of proteins that help repair damaged DNA.
  • Results from a study of olaparib in women with BRCA-mutant, high-risk, early breast cancer showed that adjuvant treatment significantly prolonged invasive disease-free and distant disease-free survival compared with placebo.
  • Adjuvant olaparib for BRCA-mutant early breast cancer is currently under review by the FDA, and the patients in OlympiA continued to be followed for effects on overall survival and long-term safety.