Long-Term Benefits of Olaparib in Early-Stage Breast Cancer Confirmed After 6 Years of Follow-Up

BRCA mutation carriers with high-risk early-stage breast cancer who received the PARP inhibitor olaparib for 1 year as adjuvant therapy after primary treatment showed a marked increase in overall survival rates. These findings were shared at the 2024 San Antonio Breast Cancer Symposium (SABCS) in a presentation of the phase III OlympiA trial's third interim analysis .

For the treatment of high-risk, BRCA mutation-positive early-stage breast cancer, the drug Lynparza, containing olaparib, received FDA approval in March 2022.

6-Year Follow-Up Results

The benefits of olaparib were clearly seen in both triple-negative breast cancer (TNBC) and estrogen receptor (ER)-positive subtypes. These results were obtained with a median follow-up of 6.1 years, and follow-up will continue until 2029.

High-Risk Criteria According to the OlympiA Trial

Significant Difference in Survival Rates

Treatment with olaparib achieved, in terms of invasive disease-free survival (IDFS, invasive disease–free survival) and distant disease-free survival, a 35% reduction in risk .

At 6 years of follow-up:

• Invasive disease-free survival rate: 79.6% in the olaparib group and 70.3% in the placebo group.

• Distant disease-free survival rate: 83.5% in the olaparib group and 75.7% in the placebo group.

In addition, treatment with olaparib lowered the risk of death by 28% and improved overall survival. At 6 years, overall survival rates were 87.5% in the olaparib group and 83.2% in the placebo group.

The Importance of Long-Term Follow-Up

These data demonstrate the substantial benefits of olaparib treatment for patients with high-risk breast cancer carrying BRCA1 or BRCA2 mutations. BRCA testing has become particularly important in treatment planning:

The long-term effectiveness of olaparib in this patient group provides a critical clue for early diagnosis, appropriate treatment planning, and selecting treatment at the optimal time.

Study Design and Findings

OlympiA was a multicenter, double-blind, placebo-controlled phase III trial involving a total of 1836 patients. After completing primary treatments such as chemotherapy, surgery, and radiotherapy, participants were randomly assigned to receive either olaparib or placebo for 1 year.

• Median age: 42.

• BRCA mutation profile: 70% BRCA1 and 30% BRCA2 mutations.

• Proportion of premenopausal patients: 60%.

• Mastectomy rate: 75%.

The median follow-up was 6 years, with a maximum follow-up of 9.6 years.

Subgroup Findings and ER-Positive Patients

The benefits of olaparib were clearly seen across all subgroups, including ER-positive patients. Its effectiveness in patients who were both ER-positive and BRCA-positive was particularly noteworthy:

ER-positive patients generally face a risk of later recurrence and therefore require longer follow-up. However, the available data demonstrate that olaparib is also effective in this group.

Risks of Secondary Cancers

Regarding adverse effects, the rate of developing a secondary (new) cancer was 4.9% in the olaparib group and 7.5% in the placebo group. Four cases of acute myeloid leukemia or myelodysplastic syndrome were reported in the olaparib group and six in the placebo group. These findings may indicate a potential benefit of olaparib in reducing BRCA-associated cancer risk.

These phase III data provide new information about the long-term benefits and adverse-effect profile of olaparib. The findings are particularly encouraging for ER-positive patients, because approximately half of these patients face a risk of recurrence after 5 years. These data will guide doctors in treatment selection.

Conclusion

The latest OlympiA trial data have once again demonstrated the effectiveness and safety of olaparib as adjuvant treatment for patients with high-risk breast cancer carrying BRCA mutations. These findings represent a critical step toward personalizing adjuvant treatment strategies and selecting appropriate treatment early through BRCA testing.