2SPD-009 Analysis of olaparib and talazoparib as possible therapeutic alternatives in advanced breast cancer and a germline BRCA mutation

BackgroundTo date, the main treatment in advanced breast cancer (ABC) with BRCA mutation is a non-specific chemotherapy of the physician’s choice.PurposeTo establish whether olaparib and talazoparib can be declared equivalent therapeutic alternatives (ETA) in patients with ABC and a BRCA mutation, through an indirect treatment comparison (ITC) using a common comparator.Material and methodsA bibliographic search was conducted to identify a phase III clinical trial with olaparib or talazoparib in a similar ABC population (with BRCA mutation), duration and endpoints. An ITC was done according to Bucher’s method, using the ITC calculator from the Canadian Agency for Health Technology Assessment. Physician’s choice (capecitabine, eribulin or vinorelbine) was used as a comparator. Delta value (Δ), maximum acceptable difference as a clinical criterion of no-inferiority, was set at 0.650 (and its inverse, 1.538). If the 95% CI deviated from the delta margin, this probability was calculated using the Shakespeare method.ResultsClinical trials included were: open-label, randomised, HER 2-negative, capecitabine, eribulin or vinorelbine as comparator, ECOG 0–1, pretreated with taxane, anthracycline or both, and if platinum was used without progression to this one. The primary end point was radiologic progression-free survival (PFS). Two trials were included, one of each drug. Both of them were open-label trials, randomised, in patients with HER2-negative ABC, ECOG 0–1 and pretreated with taxane, anthracycline or both. Differences were found in the percentage of patients with ECOG 0–1 (olaparib 72.2% vs. talazoparib 53.3%), excepting this characteristic the population of both studies was similar. The results of each trial, as well as the ITC conducted, are summarised in the following table 1:Abstract 2SPD-009 Table 1ReferencePFS: HR (95% CI) Olaparib0.58 (0.43–0.80)Talazoparib0.54 (0.41–0.71)ITC1.074 (0.71–1.626)The 95% CI was broad (high level of uncertainty) and exceeds the equivalence margin, and the probability of a result falling out the delta margin was