Indirect treatment comparison of the efficacy and safety of olaparib 300 mg tablets BID and talazoparib 1 mg once daily in the treatment of patients with germline BRCA-mutated (gBRCA) HER2-negative metastatic breast cancer.

e12570 Background: PARP inhibitor treatment with olaparib or talazoparib has been shown to improve progression-free survival (PFS) versus chemotherapy treatment of physician’s choice in patients with germline BRCA-mutated (gBRCA) HER2-negative metastatic breast cancer. In the absence of head-to-head evidence, an indirect treatment comparison (ITC) analysis was performed to simulate the comparative efficacy and safety of alternative PARP treatment in this setting. Methods: Bayesian fixed effects ITCs of data published for OlympiAD (NCT02000622) and EMBRACA (NCT01945775) was conducted using the gemtc package in R. Efficacy analyses were performed on the primary endpoint of PFS by blinded independent central review. Safety analyses included the odds ratio (OR) of adverse event (AE)-related discontinuations, and common AEs of any grade reported in each study. All analyses compared olaparib with talazoparib. Results: Efficacy analyses show no significant difference in PFS across treatments (PFS hazard ratio of 1.09, 95% credible interval [0.72; 1.65]). Safety analyses predict differences in AEs across PARP treatment, including hematological events, alopecia, nausea and vomiting (Table). No difference in AE-related discontinuations was observed (0.93 [0.25–3.42]). Conclusions: Results of the ITC suggest that olaparib and talazoparib are equally efficacious on PFS, and differ in AE risk profile, with olaparib predicted to have fewer common hematological and alopecia events, but an increased risk of nausea and vomiting versus talazoparib. Observed differences require confirmation in comparative studies. Limitations of the analysis include heterogeneity in study design, reporting of AEs, and mix of chemotherapies used in the control arm of the studies. [Table: see text]