Iniparib administered weekly or twice-weekly in combination with gemcitabine/carboplatin in patients with metastatic triple-negative breast cancer
A phase II randomized open-label study with pharmacokinetics
Purpose Metastatic triple-negative breast cancer (TNBC) is a phenotypic breast cancer subgroup with a very poor prognosis,
despite standard treatments. Combined twice-weekly iniparib and gemcitabine/carboplatin (GC+tw-iniparib) showed
benefit over gemcitabine/carboplatin in a randomized phase II trial, and a phase III was initiated comparing these regimens.
The present phase II study was initiated to compare GC+tw-iniparib with a more practical once-weekly schedule (GC+winiparib)
Methods Metastatic TNBC patients were randomized to receive iniparib weekly (11.2 mg/kg on days 1 and 8) or twiceweekly (5.6 mg/kg on days 1, 4, 8, and 11) with gemcitabine (1000 mg/m2) and carboplatin (area under the curve 2 on days 1 and 8), every 3 weeks. The primary endpoint was the overall response rate (ORR). Pharmacokinetics of iniparib and its two metabolites were analyzed.
Results A total of 163 patients were randomized, 82 GC+w-iniparib and 81 GC+tw-iniparib. Demographic and baseline characteristics were well balanced. ORR was 34.1% (95% CI 23.9–44.4%) vs. 29.6% (95% CI 19.7–39.6%) and median progression-free survival was 5.5 months (95% CI 4.2–5.7) vs. 4.3 months (95% CI 3.0–5.8) for GC+w-iniparib and GC+twiniparib, respectively. Safety was similar across treatment arms in terms of event severity and type. Iniparib plasma concentrations and exposure were two-fold higher with w-iniparib compared to tw-iniparib. Iniparib and its metabolites were cleared rapidly with a terminal half-life of < 1 h, without accumulation.
Conclusions Despite a doubled maximum concentration with weekly iniparib, no detectable differenc
|Keywords||Iniparib · Metastatic triple-negative breast cancer · Pharmacokinetics · Administration schedule|
|Persistent URL||dx.doi.org/10.1007/s10549-019-05305-w, hdl.handle.net/1765/118954|
|Journal||Breast Cancer Research and Treatment|
Diéras, V, Bonnefoi, H, Alba, E, Awada, A, Coudert, B, Pivot, X, … Verweij, J. (2019). Iniparib administered weekly or twice-weekly in combination with gemcitabine/carboplatin in patients with metastatic triple-negative breast cancer. Breast Cancer Research and Treatment, 177(2), 383–393. doi:10.1007/s10549-019-05305-w