Sustained benefit of adjuvant olaparib in women with germline BRCA1- and BRCA2- -associated high-risk HER2-negative early breast cancer: Updated results from the OlympiA phase III trial.

The randomised phase III OlympiA trial (NCT02032823) compared 1 year of adjuvant olaparib (oral poly-(ADP-ribose) polymerase [PARP] inhibitor) to placebo in 1,836 patients with pathogenic/likely pathogenic BRCA1 or BRCA2 (gBRCApv) germline variants and high-risk human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (BC). Previous interim analyses (IA) demonstrated statistically significant improvements in invasive disease-free survival (IDFS), distant disease-free survival (DDFS) and overall survival (OS), irrespective of hormone receptor status, prior platinum, timing of prior chemotherapy or type of gBRCApv. Herein are the results of the third pre-specified IA with a median follow-up (MFU) of 6.1 years. Descriptive analyses are presented for the primary endpoint IDFS, and key secondary endpoints of DDFS and OS. Estimates of the hazard ratio (HR) based on the stratified Cox's Proportional Hazards Model and 95% confidence intervals (CI) are presented with yearly event rates up to 6.1 years MFU. Safety analyses included AESIs. Olaparib benefits were maintained in IDFS [HR=0.65 (95% CI: 0.53, 0.78)], DDFS [HR=0.65 (95% CI: 0.53, 0.81)] and OS [HR=0.72 (95% CI: 0.56, 0.93)]. The 6-year OS for olaparib vs. placebo was 87.5% vs. 83.2% [Difference 4.4% 95% CI: 0.9%, 6.7%]. Olaparib benefit was consistent across all key subgroups, including patients with high-risk hormone receptor-positive disease. There were fewer BRCA-associated new breast and ovarian/fallopian tube cancers and no increase in AESI risks (6.3% versus 9.3%), including myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) (0.4% versus 0.7%), with olaparib versus placebo. At 6.1 years MFU, 1 year of adjuvant olaparib after (neo)adjuvant chemotherapy demonstrates ongoing clinically meaningful improvements in IDFS, DDFS and OS in patients with gBRCApv and high-risk, HER2-negative early BC, with acceptable toxicity and without increased risk of MDS/AML. These data continue to provide support for adjuvant olaparib in the treatment of gBRCApv-associated high-risk, HER2-negative early BC.