200P OlympiAD: Exploratory analysis of olaparib vs capecitabine in patients with germline BRCA-mutated (gBRCAm) metastatic breast cancer (mBC)

Following the introduction of olaparib into the early and mBC settings, there have been questions about optimal sequencing and decision-making between olaparib and capecitabine. While there are no data to support decisions in the early setting, the phase III randomised OlympiAD trial (NCT02000622) showed significantly longer PFS with olaparib vs single-agent chemotherapy of the physician’s choice (TPC; capecitabine, eribulin, or vinorelbine), in patients with gBRCAm HER2-negative mBC who had received ≤2 previous chemotherapy regimens for metastatic disease (Table). We report an exploratory post-hoc analysis of OlympiAD comparing the efficacy of olaparib vs capecitabine from the primary analysis (data cut-off 9 Dec 2016). Patients were randomised to olaparib 300 mg twice daily (n=205) or TPC (n=97; of which n=43 received capecitabine 2500 mg/m2 for 14 days every 21 days). Analyses were conducted in all patients and those with triple-negative BC (TNBC). Post-hoc analyses compared olaparib vs capecitabine in capecitabine-eligible patients (i.e., olaparib patients who would have received capecitabine if they had been randomised to TPC). The primary endpoint was PFS by blinded independent central review. In all analysed populations, olaparib was associated with improved median PFS vs TPC or capecitabine (Table). Safety was aligned with published data.Table: 200PPFS by blinded independent central reviewPopulationOlaparibComparator (TPC or capecitabine)HR (95% CI)Events n/N (%)Median, monthsEvents n/N (%)Median, monthsAll patientsOlaparib vs TPC163/205 (79.5)7.071/97 (73.2)4.20.58 (0.43–0.80); p=0.0009*Capecitabine-eligible patient subgroup: Olaparib vs capecitabine72/95 (75.8)8.232/43 (74.4)4.20.55 (0.34–0.89)Patients with TNBCOlaparib vs TPC81/102 (79.4)5.640/48 (83.3)2.90.43 (0.29–0.63)Capecitabine-eligible patient subgroup: Olaparib vs capecitabine34/44 (77.3)5.920/23 (87.0)2.90.32 (0.16– 0.64)∗OlympiAD was powered to assess the PFS benefit between olaparib vs TPC in this population. Open table in a new tab ∗OlympiAD was powered to assess the PFS benefit between olaparib vs TPC in this population. Olaparib was associated with longer PFS vs TPC or capecitabine with an acceptable safety profile in gBRCAm HER2-negative mBC. These results may aid in the optimal treatment selection for patients with gBRCAm BC. Limitations included the exploratory nature of the analysis and small sample sizes.