Phase II Trials of Iniparib (BSI-201) in Combination with Gemcitabine and Carboplatin in Patients with Recurrent Ovarian Cancer
Mené sur des patientes atteintes d'un cancer de l'ovaire récidivant, cet essai multicentrique de phase II évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité d'un traitement combinant iniparib (un inhibiteur de PARP), gemcitabine et carboplatine
Background: Iniparib (BSI-201), a novel anticancer agent thought to have poly(ADP-ribose) polymerase (PARP) inhibitory activity and synergy with both gemcitabine and carboplatin (GC) was evaluated in 2 cohorts with GC. Methods: Parallel multicenter, single-arm, phase II studies using a Simon two-stage design. Eligible patients had a histological diagnosis of epithelial ovarian carcinoma, fallopian tube cancer, or primary peritoneal carcinoma and demonstration of platinum-sensitive (≥6 months [mo]) or -resistant disease (relapse 2-6 mo post-platinum). Carboplatin (AUC 4 IV day 1), gemcitabine (1000 mg/m2 IV days 1 and 8), and iniparib (5.6 mg/kg IV days 1, 4, 8, and 11) were given on a 21-day cycle. Results: The overall response rate (ORR RECIST 1.0) in platinum sensitive disease was 66% (95% CI, 49-80) with a higher response rate in the 15 pts with germline BRCA mutations (gBRCAmut) (73%). Median PFS was 9.9 (95% CI, 8.2-11.3) months. In the platinum resistant population the ORR was 26% (95% CI, 14-42), however in the 11 pts for whom BRCA mutation was present, the best overall response was PR in 5 (46%). Median PFS was 6.8 months (range, 5.7-7.7 months). Notably, among the 17 CA-125-response-evaluable patients who did not achieve tumor response, 7 (41.2%) patients had a CA125 response, and 93% has clinical benefit (CR + PR + SD). The GCI combination was generally well tolerated despite a high incidence of thrombocytopenia and neutropenia, with no new toxicities. Conclusions: Given the subsequent lack of efficacy demonstrated for iniparib in breast cancer, these are studies of GC and demonstrate a higher than traditionally appreciated activity in patients with platinum-sensitive and -resistant recurrent ovarian cancer, especially in patients that harbor a BRCA mutation, resetting the benchmark for efficacy in phase II trials. (ClinicalTrials.gov Identifiers: NCT01033292 & NCT01033123).