• OlympiAD extended follow-up for overall survival and safety: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer

      Robson, M; Im, SA; Senkus, E; Xu, BH; Domchek, S; Masuda, N; Delaloge, S; Li, W; Tung, N; Armstrong, Anne C; et al. (2020)
      Background: In the OlympiAD study, olaparib showed a clinically meaningful benefit in progression-free survival compared with chemotherapy treatment of physician's choice (TPC) in patients with a germline BRCA1 and/or BRCA2 mutation (BRCAm) and HER2-negative metastatic breast cancer (mBC; Robson N Engl J Med 2017). Final prespecified median overall survival (OS) at 64% data maturity was 19.3 months with olaparib versus 17.1 months with TPC (Robson Ann Oncol 2019). At this time, 26 patients continued to receive olaparib, with none continuing to receive TPC as assigned. After consenting to a protocol amendment, post hoc follow-up of patients for survival status and serious adverse events continued. Patients and methods: OlympiAD is a Phase III, randomized, controlled, open-label trial (NCT02000622). Patients with a germline BRCAm and HER2-negative mBC who had received ?2 prior lines of chemotherapy for mBC were randomized to olaparib tablets (300 mg twice daily) or predeclared TPC (capecitabine, vinorelbine or eribulin). Extended OS and safety follow-up were exploratory endpoints; the study was not powered to detect an OS benefit or treatment effect between subgroups. The overall hazard ratio (HR) was estimated using a stratified log-rank test, and a single Cox proportional hazards model was used for analyses in prespecified subgroups. Results: Of patients randomized to olaparib (n=205) or TPC (n=97), 160 (78.0%) and 80 patients (82.5%) respectively had withdrawn from the study (majority due to death), and seven and eight patients, respectively, did not participate in the extended follow-up. At data cut-off (March 3, 2019), 223 patients had died (73.8% data maturity), 24 (11.7%) patients from the olaparib arm and nine patients (9.3%) from the TPC arm were continuing the study off treatment, no patients were continuing to receive TPC as assigned. Fourteen patients (6.8%) were continuing olaparib at this time; in this small number of patients at baseline their median age was 42.5 years, 42.9% had not received prior chemotherapy for mBC, 57.1% were TNBC, 50.0% had a BRCA1 mutation, 42.9% had liver metastasis and 57.1% had ?2 metastatic sites. Median follow-up was 18.9 months in the olaparib arm and 15.5 months in the TPC arm (40.7 and 29.2 months in censored patients, respectively). OS and landmark analyses for the overall population and prespecified key subgroups are reported in the Table. Of patients who discontinued study treatment, 2.0% in the olaparib arm and 11.3% in the TPC arm received subsequent PARP inhibitors, and 42.4% and 48.5%, respectively, received subsequent platinum chemotherapy. Median total study treatment duration was 251 days in the olaparib arm versus 105 days in the TPC arm, with 8.8% of olaparib patients receiving treatment for >3 years versus no TPC patients. During the extended follow-up period, there were no new serious adverse events suspected to be related to olaparib treatment, including no reports of myelodysplastic syndrome/acute myeloid leukemia.