OlympiAD Trial: Olaparib in Metastatic Breast Cancer With Germline BRCA Mutation
As reported in the Plenary Session at the 2017 ASCO Annual Meeting and in The New England Journal of Medicine by Robson et al, the phase III OlympiAD trial showed that the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib (Lynparza) prolonged progression-free survival vs standard therapy in patients with HER2-negative metastatic breast cancer with a germline BRCA mutation.
Study Details
In the open-label trial, 302 patients were randomized 2:1 between April 2014 and November 2015 to receive oral olaparib at 300 mg twice daily (n = 205) or standard therapy with physician’s choice of single-agent chemotherapy with capecitabine (n = 41), eribulin (Halaven; n = 34), or vinorelbine (n = 16) in 21-day cycles. Six patients in the control group did not receive the assigned treatment. Patients could have received no more than two previous chemotherapy regimens for metastatic disease. The primary endpoint was progression-free survival on independent central review in the intention-to-treat population.
For the olaparib and control groups, the patients had a median age of 44 and 45 years, 2% were male, 65% were white and 32% and 29% were Asian, 57% and 53% had BRCA1 and 41% and 47% BRCA2 mutation (2% and 0% had both), 50% had hormone receptor–positive disease and 50% had triple-negative disease, 71% had prior chemotherapy for metastatic disease, and 29% and 27% had received prior platinum therapy.
Improved Progression-Free Survival
Median follow-up was 14.5 months in the olaparib group and 14.1 months in the control group. Median progression-free survival was 7.0 months vs 4.2 months (hazard ratio [HR] = 0.58, P < .001).
A sensitivity analysis excluding the six control group patients who did not receive assigned treatment showed similar results (HR = 0.58, P < .001). Objective response rates were 59.9% in 167 olaparib patients vs 28.8% in the 66 control group patients with measureable disease at baseline. At the time of the primary analysis, median overall survival was 19.3 months vs 19.6 months (HR = 0.90, P = 0.57); more patients in the control group received PARP inhibitors, platinum-based therapy, or other cytotoxic chemotherapy after disease progression.
Adverse Events
Grade ≥ 3 adverse events occurred in 37% of the olaparib group and 51% of the control group, with the most common events in the olaparib group being anemia (16% vs 4%), neutropenia (9% vs 26%), and decreased white blood cell count (3% vs 10%). Dose reductions were most frequently due to anemia in the olaparib group (14%) and to palmar-plantar erythrodysesthesia in the control group (8%). Adverse events led to discontinuation of treatment in 4.9% (2.0% due to anemia) vs 7.7% (2.2% due to anemia).
The investigators concluded: “Among patients with HER2-negative metastatic breast cancer and a germline BRCA mutation, olaparib monotherapy provided a significant benefit over standard therapy; median progression-free survival was 2.8 months longer and the risk of disease progression or death was 42% lower with olaparib monotherapy than with standard therapy.”
The study was funded by AstraZeneca.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
