For women with high-risk, BRCA-positive breast cancer, 1 year of adjuvant treatment with the PARP inhibitor olaparib following primary treatment continued to improve overall survival compared with placebo, according to the third interim analysis of the phase III OlympiA trial presented at the 2024 San Antonio Breast Cancer Symposium.1 The benefits of olaparib were evident in patients with triple-negative breast cancer and in those with estrogen receptor (ER)-positive breast cancer, after a median of 6.1 years. Follow-up of OlympiA will continue until 2029.
Olaparib is approved by the U.S. Food and Drug Administration for adjuvant therapy in specific patients with HER2-negative BRCA-positive breast cancer, and these long-term data provide greater reassurance about the benefits of this strategy.
Olaparib significantly reduced the risk of invasive disease–free survival and distant disease–free survival by 35% each. At the 6-year mark, 79.6% of the olaparib-treated group vs 70.3% of the placebo group were free of invasive disease; and 83.5% of the olaparib-treated group vs 75.7% of the placebo group were free of distant recurrence. Moreover, adjuvant treatment with olaparib achieved a 28% reduction in the risk of death, with no increase in the risk of developing secondary myelodysplastic syndrome or acute myeloid leukemia, both of which are a concern in this setting.
Judy E. Garber, MD, MPH
“Results of OlympiA examining 1 year of the oral PARP inhibitor olaparib after completion of standard therapy for higher risk breast cancer in individuals with pathogenic germline BRCA1 or BRCA2 mutations provide further support for olaparib’s benefits in this population,” said presenting author Judy E. Garber, MD, MPH, Chief of the Division of Cancer Genetics and Prevention at Dana-Farber Cancer Institute, Boston.
“The ongoing data from the OlympiA trial are reassuring in the observations of persistent and increasing benefits for these breast cancer patients in the follow-up phases, improving not only protection against recurrence, but also overall survival as well. This demonstration of efficacy makes it more important than ever that we be able to identify individuals who might benefit when they begin treatment, so we can plan to introduce olaparib to their care at the most opportune moments,” Dr. Garber told listeners.
Study Details and Key Results
OlympiA is a multicenter, double-blind, placebo-controlled phase III trial that randomly assigned 1,836 patients with stage II–III, BRCA-positive, HER2-negative breast cancer to receive either 1 year of adjuvant treatment with olaparib or placebo after completion of primary treatment with chemotherapy, surgery, and radiation therapy. The average age of participants was 42 years. A total of 70% had BRCA1 mutations and 30%, BRCA2. About 60% were premenopausal, and 75% had a mastectomy.
At a median follow-up of 6 years (maximum follow-up 9.6 years), the absolute difference in invasive disease–free survival between the two arms was 9.4%, favoring the addition of olaparib. The benefits of PARP inhibition were observed across all subgroups.
The absolute difference in distant disease–free survival between the two treatment arms was 7.8%. Additionally, a 4.4% absolute difference in overall survival favored olaparib, with a 38% reduction in the risk of death. The 6-year overall survival rate was 87.5% in the olaparib group vs 83.2% in the placebo group.
“With further follow-up, the benefits of olaparib continue,” Dr. Gerber noted.
There were fewer new primary malignancies in the olaparib-treated group than in the placebo group (4.9% vs 7.5%). There were fewer cases of breast cancer or primary ovarian or fallopian tube cancers as well. Regarding side effects of interest, there were four cases of myelodysplastic syndrome/acute myeloid leukemia in the olaparib-treated group vs six in the placebo arm.
“The data are still being analyzed to determine whether olaparib reduces the risk of cancers related to BRCA1 or BRCA2. People undergo prophylactic surgeries at different times, and this increases the complexity of the analysis,” Dr. Garber said.
Subgroup Findings
As mentioned, the benefits of olaparib were seen across all subgroups, including the ER-positive subset. “Olaparib reduced the risk of new primary tumors, and there is no concern about secondary tumors. This study highlights the importance of BRCA testing for treatment planning,” Dr. Garber emphasized.
Regarding the positive outcomes seen in the ER-positive patients, “there is good evidence for the activity of olaparib in this subgroup. Many clinicians have been giving olaparib first followed by a CDK4/6 inhibitor, because you can’t give them together because of myelosuppression. We have good reason to state that olaparib has efficacy in ER-positive BRCA-positive breast cancer. We should not limit the use of this drug to ER-negative patients,” she continued. “That said, 6 years of follow-up is relatively short, and longer follow-up is critical for ER-positive patients, who tend to recur later.”
Kate Lathrop, MD
EXPERT POINT OF VIEW
Kate Lathrop, MD, of Mays Cancer Center, UT Health San Antonio MD Anderson Cancer Center, shared these comments on the OlympiA study with The ASCO Post:
“These promising phase III data with long-term follow-up confirm the benefit of olaparib in this setting and provide a further review of toxicity. It is reassuring to see the long-term benefit, particularly in the estrogen receptor–positive patients, because about half will recur beyond 5 years. We are still seeing a long-term consistent benefit for adjuvant olaparib in these patients. These data will help us make therapeutic choices. The persistent benefit of olaparib will guide conversations where the choice is between a CDK4/6 inhibitor and the PARP inhibitor olaparib,” she said.
DISCLOSURE: OlympiA was funded by AstraZeneca and Merck. Dr. Garber reported no conflicts of interest. Dr. Lathrop has served in a consulting role with TeraSera Pharmaceuticals as well as continuing medical education or educational activities with ASCO, Eli Lilly & Co, Encore Education, and Pfizer.
REFERENCE
- Garber J: OlympiA—Phase 3, multicenter, randomized placebo-controlled trial of adjuvant olaparib after (neo)adjuvant chemotherapy in patients with germline BRCA1/BRCA2 pathogenic variants and high-risk HER2-negative primary breast cancer: Longer-term follow-up. 2024 San Antonio Breast Cancer Symposium. Abstract GS1-09. Presented December 11, 2024.
