The European Commission has approved olaparib (Lynparza) for the treatment of adult patients with germline BRCA1/2
-mutant, HER2-negative locally advanced or metastatic breast cancer.
The decision is based on findings from the phase III OlympiAD trial, in which the PARP inhibitor reduced the risk of disease progression or death by 42% compared with chemotherapy in patients with germline BRCA
-mutant, metastatic disease.
With the indication, patients must have been previously treated with an anthracycline and a taxane in the neoadjuvant or metastatic setting unless they were ineligible to receive them. Additionally, those with hormone receptor (HR)–positive breast cancer must have progressed on or following endocrine therapy or be ineligible for the treatment, according to AstraZeneca, which codevelops the PARP inhibitor with Merck (MSD).
“With this approval, Lynparza provides patients throughout the EU with a targeted and oral chemotherapy-free treatment option for a difficult-to-treat cancer,” Dave Fredrickson, executive vice president, oncology, AstraZeneca, said in a press release. “It also reinforces the importance of testing for biomarkers including BRCA
, hormone receptor and HER2 expression, helping physicians to make the most informed treatment decisions for patients.”
In the international, multicenter, open-label, phase III OlympiAD study, investigators randomized 302 patients to 300 mg of olaparib twice daily (n = 205) or physician’s choice of chemotherapy (n = 97), which included capecitabine, eribulin (Halaven), or vinorelbine. The trial was conducted in 19 countries across Europe, Asia, North America, and South America.
To be eligible for enrollment, patients must have had germline BRCA1
- or BRCA2
-mutant, HER2-negative disease. All patients were previously treated with an anthracycline, unless it was contraindicated, and taxane chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Those with metastatic disease (71% of the overall population) received ≤2 prior lines of chemotherapy and those with HR-positive breast cancer received ≥1 endocrine therapy and experienced disease progression.
The trial permitted prior treatment with platinum chemotherapy in the neoadjuvant, adjuvant, or metastatic setting, which was 28% of overall patients. Those who did receive prior platinum regimens must have completed treatment within 12 months of starting on the OlympiAD trial.
The median patient age was approximately 45, and about one-third of patients were non-white (mainly Asian).
Results showed that the median progression-free survival (PFS) was 7.0 months with olaparib compared with 4.2 months with chemotherapy, demonstrating a statistically significant improvement (HR, 0.58; 95% CI, 0.43-0.80; P
= .001). The PFS analysis occurred after 163 events in the olaparib cohort and 71 events in the chemotherapy group.
At 12 months, 25.9% of the patients in the olaparib group and 15.0% of the patients in the standard-therapy arm were free from progression or death. Overall, 52% of patients had a second progression event or had died after a first progression event. The median time from randomization to a second progression event or death following a first progression event was 13.2 months in the olaparib group and 9.3 months in the standard-therapy arm (HR, 0.57; 95% CI, 0.40-0.83; P
By the time of the primary analysis, 94 patients (45.9%) in the olaparib group and 46 patients (47.4%) in the standard-therapy group had died. The median time to death was 19.3 months and 19.6 months in the olaparib and standard-therapy groups, respectively. The overall survival was similar between the two groups (HR, 0.90; 95% CI, 0.63-1.29; P
According to blinded independent central review, 100 of the 167 patients who had measurable disease responded to treatment. The response rate was 59.9% (95% CI, 52.0-67.4) in the olaparib arm versus 28.8% (95% CI, 18.3-41.3) in the chemotherapy group. Investigators observed complete response (CR) in 9.0% of the patients who had measurable disease in the olaparib group and in 1.5% in the standard-therapy arm.
Additionally, the overall response rates were 52% and 23% for olaparib and chemotherapy, respectively. The median duration of response was 6.4 months in the olaparib group and 7.1 months in the standard-therapy group, and the median time to onset of response was 47 days and 45 days, respectively.
Regarding safety, the most common adverse events (≥20%) in the olaparib arm were nausea (58%), anemia (40%), fatigue (including asthenia; 37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%), and headache (20%). The treatment discontinuation rates were 5% and 8% for olaparib and chemotherapy, respectively.