New data from the OlympiA clinical trial presented at the 2024 San Antonio Breast Cancer Symposium (SABCS) show that the PARP inhibitor olaparib (Lynparza) significantly improves survival in patients with high-risk, BRCA-positive, HER2-negative early breast cancer. The findings, after a median follow-up of 6.1 years, further support the drug’s use as an adjuvant therapy after standard treatments like chemotherapy, surgery, and radiation.
“The OlympiA trial examines adding one year of the oral PARP inhibitor olaparib after completion of standard treatment for higher risk breast cancer in individuals with pathogenic germline BRCA variants,” said Judy E. Garber, MD, chief of the division of cancer genetics and prevention at Dana-Farber Cancer Institute and one of the principal investigators of the OlympiA trial. “Data from the third prespecified interim analysis presented here provides further support for olaparib’s benefits in patients with high-risk, HER2-negative breast cancer with germline mutations in BRCA1 or BRCA2.”
Launched in 2014, the OlympiA trial led to the approval of olaparib for use after surgery in certain patients with early-stage, high-risk breast cancer. The study included 1,836 patients with germline BRCA1/2 mutations who were randomized to receive either olaparib or placebo for one year following the completion of standard treatment. The results demonstrated that olaparib reduced the risk of recurrence or death by 35%, with patients treated with the drug showing significantly better survival rates than those on placebo.
After the followup at six years, the data show that 79.6% of the olaparib group remained free of invasive recurrence, compared to 70.3% in the placebo group. For distant recurrence, the difference was even more pronounced, with 83.5% of olaparib patients remaining free of distant recurrence versus 75.7% in the placebo cohort.
“This ongoing data from the OlympiA trial is reassuring, showing not only persistent protection against recurrence but also overall survival improvements,” said Garber. “This demonstration of efficacy underscores the importance of identifying individuals who could benefit from olaparib as early as possible.”
Further data that showed fewer secondary cancers in the olaparib group versus placebo (38 and 57, respectively) were encouraging, as was the fact that there were an equal number of pregnancies in both cohorts, providing important information on the effects in younger patients. The data also point the way to potentially expanding which patients could receive the PARP inhibitor.
“These data highlight the safety of olaparib and, therefore, the possibility of moving PARP inhibitors to the treatment of BRCA-associated breast cancers that are lower risk,” noted Garber. “It also allows us to consider the very preliminary possibility of a safe and effective oral agent that could be developed for cancer interception—to be given intermittently to eliminate cells in BRCA mutation carriers that have begun to transform toward several types of malignancy.”
PARP inhibitors, like olaparib, work by targeting the Poly(ADP-ribose) polymerase (PARP) enzyme, which is involved in repairing DNA damage. In cancers with BRCA1/2 mutations, the DNA repair system is already compromised, and PARP inhibitors prevent further repair, leading to cancer cell death.
Recent studies have also explored extending the use of PARP inhibitors to treat other types of cancer, such as ovarian and prostate cancers, since forms of these cancers share similar genetic mutations, like BRCA and PALB2 alterations. Based on these studies, PARP inhibitors have already been approved for metastatic BRCA-positive ovarian cancer, and their use is expanding into other tumor types.
Since patients often develop resistance to PARP inhibitors, studies are also ongoing to examine the efficacy of including them in combination therapies with other treatment methods such as chemotherapy, radiotherapy, and CDK 4/6 immune checkpoint inhibitors. Ongoing trials are also seeking to find out if PARP inhibitors can be effective against lung cancer, pancreatic cancer, head and neck cancer, and glioblastoma.
