Among ovarian cancer patients with early relapse after platinum chemotherapy, there is no convincing active treatment. In preclinical studies, we previously demonstrated promising activity of Navitoclax (ABT-263), an anti-apoptotic inhibitor of Bcl-2 family, in ROC tumors, suggesting a potential action in platinum resistant patients. In this prospective multicentric phase II study, we evaluated the efficacy of Navitoclax monotherapy in heavily pretreated ROC patients.
This study included high grade serous patients with platinum resistance. Navitoclax was orally administered at 150 mg/day during a lead in period (7 to 14 days) and then increased to 250 mg in the absence of dose-limiting thrombocytopenia (
From January to September 2016, 47 patients were included in 13 institutions and 46 patients were analysed: 44 ovarian carcinomas, 1 peritoneal carcinoma and 1 fallopian tube, median age 63 (38-80); BRCA1/2 mutations (n = 7), negative (n = 25) and unknown (n = 14). The median number of prior treatment lines was 4 (2-12). PFS was 50 days [6-234] with 1 partial response (PR), 15 stable diseases (SD). Thrombocytopenia was the major expected side effect, with G3 (n = 11) and G4 (n = 1) leading to maintain the dose at 150 mg for 8 patients and to treatment discontinuation for 3 patients. Neither significant bleeding nor toxic death was observed. 26 patients were treated after progression, 23 with chemotherapy (10 receiving platinum agent): among the 21 evaluable patients, 1 PR and 8 SD were observed, including 6 patients treated with platinum, with 3 long responders (7 to 9 months). No BRCA mutation was observed among the responders.
Navitoclax monotherapy had modest activity without unacceptable toxicity. However, as shown by response to treatment after progression, Navitoclax may reverse platinum resistance in ROC patients. Complementary biological data in progress may help select patients who could benefit from Navitoclax.
Clinical trial identification
EudraCT number: 2015-000193-35 Clinical Trial Number: N° NCT02591095
Legal entity responsible for the study
Centre François Baclesse - CAEN
The French Cancer Research Hospital Program in 2011 & the Mariapia Bressan award in GINEGEPS 2014 Drug supply has been provided by Abbvie Laboratory
All authors have declared no conflicts of interest.