EU Approves Adjuvant Olaparib for BRCA-Mutated, HER2-Negative Early Breast Cancer

Author(s):

The European Commission has approved olaparib as a single agent or in combination with endocrine therapy for the adjuvant treatment of adult patients with germline BRCA1/2-mutated, HER2-negative, high-risk early breast cancer.

Andrew Tutt, MD, PhD

The European Commission has approved olaparib (Lynparza) as a single agent or in combination with endocrine therapy for the adjuvant treatment of adult patients with germline BRCA1/2-mutated, HER2-negative, high-risk early breast cancer who have been previously treated with neoadjuvant or adjuvant chemotherapy.¹

The approval was based on results from the phase 3 OlympiA trial (NCT02032823), which showed that olaparib demonstrated a clinically meaningful 42% improvement in invasive disease-free survival (iDFS) vs placebo (HR, 0.58; 99.5% CI, 0.41-0.82; P < .0001).² Additionally, olaparib achieved a statistically significant and clinically meaningful improvement in overall survival (OS) vs placebo, reducing the risk of death by 32% (HR, 0.68; 98.5% CI, 0.47-0.97; P = .009). Safety was also consistent with findings from prior trials.

“Today’s approval marks a new era of care in Europe for patients with an inherited form of breast cancer,” Andrew Tutt, MD, PhD, global chair of the OlympiA trial and professor of Oncology at The Institute of Cancer Research, London and King’s College London, stated in a press release. “For patients with high-risk early-stage breast cancer, including those with germline BRCA mutations, recurrence rates remain unacceptably high, with more than one in four of these patients seeing their cancer return following surgery and systemic treatment.

“Olaparib is the first PARP inhibitor to demonstrate OS for high-risk early-stage breast cancer patients with germline BRCA mutations, and I am hopeful it will become a new standard of care.”

The multicenter, randomized, placebo-controlled OlympiA trial enrolled 1836 patients with histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast that was either triple-negative breast cancer, or endocrine receptor– or progesterone receptor–positive, HER2-negative breast cancer.³ Other key inclusion criteria were a documented germline BRCA1/2 mutation; completed adequate breast and axilla surgery; completed at least 6 cycles of neoadjuvant or adjuvant chemotherapy; and an ECOG performance status of 0 or 1.

Patients were excluded from the trial if they had any prior treatment with a PARP inhibitor, had a secondary malignancy except for non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ of the breast, stage I, grade 1 endometrial carcinoma, or other solid tumors/lymphomas without bone marrow involvement diagnosed at least 5 years prior to randomization), or had evidence of metastatic breast cancer.

Enrolled patients were randomly assigned to 300 mg of oral olaparib twice daily for 1 year (n = 921) or placebo (n = 915). The primary end point for the study was iDFS. Secondary end points included distant disease-free survival (DDFS), OS, health-related quality of life, and safety.

Additional data showed that patients in the olaparib arm had a 3-year iDFS rate of 85.9%, compared with 77.1% in the placebo arm (8.8% difference; 95% CI, 4.5%-13.0%; HR, 0.58; 99.5% CI, 0.41-0.82; P <.001). The 3-year DDFS rates were 87.5% and 80.4% in the olaparib and placebo groups, respectively (7.1% difference; 95% CI, 3.0%-11.1%; HR, 0.57; 99.5% CI, 0.39-0.83; P <.001).

The most common adverse effects (AEs) of any grade in the olaparib arm were nausea (57%), fatigue (42%), anemia (24%), vomiting (23%), headache (20%), diarrhea (18%), leukopenia (17%), neutropenia (16%), decreased appetite (13%), dysgeusia (12%), dizziness (11%) and stomatitis (10%). Approximately 10% of patients given olaparib discontinued treatment due to AEs. The most common grade 3 or higher AEs included anemia (9%), neutropenia (5%), leukopenia (3%) and fatigue (1.8%).

In March 2022, the FDA approved olaparib for the adjuvant treatment of patients with germline BRCA-mutated, HER2-negative, high-risk early breast cancer who have previously received chemotherapy either before or after surgery, also based on data from OlympiA.⁴

References

Lynparza® (olaparib) approved in the EU as adjuvant treatment for patients with germline BRCA-mutated, HER2-negative high-risk early breast cancer. News release. Merck. August 4, 2022. Accessed August 4, 2022. https://bit.ly/3zY2mre
Tutt ANJ, Garber JE, Kaufman B, et al. Adjuvant olaparib for patients with BRCA1- or BRCA2-mutated breast cancer. N Engl J Med. 2021;384(25):2394-2405. doi:10.1056/NEJMoa2105215
Olaparib as adjuvant treatment in patients with germline BRCA mutated high risk HER2 negative primary breast cancer (OlympiA). ClinicalTrials.gov. Updated June 13, 2022. Accessed August 4, 2022. https://clinicaltrials.gov/ct2/show/NCT02032823
Lynparza approved in the US as adjuvant treatment for patients with germline BRCA-mutated HER2-negative high-risk early breast cancer. News release. AstraZeneca. March 11, 2022. Accessed August 4, 2022. https://bit.ly/3tQePcn