The European Commission approved last week the oral therapy olaparib (Lynparza, AstraZeneca/MSD) for the treatment of locally advanced or metastatic breast cancer in patients who have germline BRCA1/2 mutations (gBRCAm) and are human epidermal growth factor receptor 2 (HER2) negative.
The new indication has additional stipulations.
One, patients should have been previously treated with an anthracycline and a taxane in the (neo)adjuvant or metastatic setting — unless they were unsuitable for these chemotherapies. Two, patients with hormone receptor (HR) positive disease should have progressed on or after prior endocrine therapy — unless they were unsuitable for that therapy.
Olaparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes.
The new approval was based on efficacy and safety data from the randomized, open-label, phase 3 OlympiAD trial that compared olaparib (300 mg twice daily) against physician’s choice of chemotherapy (capecitabine [Xeloda, Hoffmann-La Roche]), eribulin [Halaven, Eisai], or vinorelbine [Navelbine, Pierre Fabre]).
Patients in the olaparib group (n = 205) had a median progression-free survival (PFS) of 7 months versus 4.2 months for the chemotherapy group (n = 97) (hazard ratio [HR], 0.58; P = .0009). PFS was the primary endpoint. Additionally, the olaparib group had an objective response rate (ORR) of 52% versus 23% in the chemotherapy group.
The most common adverse reactions (≥ 20%) among study patients who received olaparib were nausea (58%), anemia (40%), fatigue (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%), and headache (20%).
Also, 5% of patients in the olaparib group discontinued treatment versus 8% in the chemotherapy group.
“With this approval, [olaparib] provides patients throughout the EU with a targeted and oral chemotherapy-free treatment option for a difficult-to-treat cancer,” said Dave Fredrickson, executive vice president, AstraZeneca, in a company press statement. He added: “It also reinforces the importance of testing for biomarkers including BRCA, HR, and HER2 expression, helping physicians to make the most informed treatment decisions for patients.”