Olaparib confers durable benefit in BRCA-mutated breast cancer
Key takeaways:
- Olaparib reduced risk for invasive and distant DFS compared with placebo.
- A lower percentage patients who received olaparib died during follow-up.
SAN ANTONIO — One year of adjuvant olaparib after standard treatment improved outcomes compared with placebo among patients with high-risk BRCA-mutated breast cancer, according to data presented at San Antonio Breast Cancer Symposium.
Results of the third prespecified interim analysis of the randomized OlympiA trial showed a durable benefit in invasive DFS — the study’s primary endpoint — with the poly(ADP)-ribose polymerase (PARP) inhibitor after more than 6 years of follow-up.
“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,” Judy E. Garber, MD, MPH, chief of the division of cancer genetics and prevention at Dana-Farber Cancer Institute, said in a press release. “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 [who] have begun to transform toward several types of malignancy.”
Background and methods
The randomized, phase 3 OlympiA trial assessed the efficacy of 1 year adjuvant olaparib (Lynparza; AstraZeneca, Merck) compared with placebo among patients with high-risk HER2-negative primary breast cancer who harbored pathogenic or likely pathogenic germline variants in BRCA1 or BRCA2 .
The study included 1,836 patients, all of whom completed neoadjuvant chemotherapy, surgery and radiation prior to the study.
Researchers randomly assigned patients to 300 mg oral olaparib twice daily (n = 921) or placebo (n = 915) for 1 year.
Data from the first prespecified interim analysis showed a statistically significant improvement in invasive DFS and distant DFS.
Data from the second prespecified interim analysis showed a statistically significant improvement in OS, with no excess acute myeloid leukemia or myelodysplastic syndrome observed.
In the third prespecified analysis, researchers evaluated invasive DFS, distant DFS and OS with the longer follow-up.
Results, next steps
After median follow-up of 6.1 years, researchers observed improvements in all outcomes in the olaparib group, including 6-year DFS (79.6% vs. 70.3%; HR = 0.65; 95% CI, 0.53–0.78) and 6-year distant DSF (83.5% vs. 75.7%; HR = 0.65; 95% CI, 0.53–0.81).
Data also showed a higher 6-year OS rate in the olaparib group (87.5% vs. 83.2%; difference = 4.4%; 95% CI, 0.9-6.7). A lower percentage of patients assigned olaparib died (11.6% vs. 15.6%).
The benefit with olaparib appeared consistent across all key subgroups, including patients with high-risk, hormone-receptor-positive disease.
Data showed fewer reported BRCA-associated cancers among patients who received olaparib, including contralateral invasive breast cancer (31 vs. 40), contralateral noninvasive breast cancer (3 vs. 4), new primary ovarian cancer (3 vs. 9) and new primary fallopian tube cancer (1 vs. 4).
Fewer patients assigned olaparib developed adverse events of special interest (6.3% vs. 9.3%).
“You always worry in a trial like this that the curves will start to come together and you won’t have a maintained benefit, but fortunately that’s not what we saw,” Garber told Healio. “The curves have continued, if anything, to separate.
“Very important to us was the fact that the subgroups continued to benefit because there’s always been worry that this might not work as well in the hormone receptor-positive group; but right now, the data show benefit in both groups.”
A fourth and final planned analysis will continue until 2029. Garber said she expects those results to show continued benefit with olaparib.
The OlympiA trial also can provide researchers with a strong patient population for further research, Garber said.
“There’s a huge panel of translational studies underway,” Garber told Healio. “Where else do you have 1,800 mutations carriers so well characterized? There are six working groups and lots of work still to come — we are not finished with OlympiA.”
Reference:
- PARP inhibition shows long-term survival benefits for patients with high-risk, BRCA-positive breast cancer (press release). Available at: https://www.dana-farber.org/newsroom/news-releases/2024/parp-inhibition-shows-long-term-survival-benefits-for-patients-with-high-risk-brca-positive-breast-cancer. Published Dec. 11, 2024. Accessed Dec. 11, 2024.
Perspective
Back to TopThese are good results for our patients. I think this is a promising trial. Seeing that benefit as we move further out in long-term follow-up is very encouraging.
PARP inhibitors are generally pretty well tolerated but they do have toxicity. Knowing what the longer-term benefit is for patients who are taking these medications is positive, because what I struggle with most in the adjuvant setting is the cytopenias if [patients] come right off of having chemotherapy and their bone marrow is already a little decreased in [its] robustness.
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Garber JE, et al. Abstract GS1-09. Presented at: San Antonio Breast Cancer Symposium; Dec. 10-13, 2024; San Antonio.