The CHIVA study: a GINECO randomized double blind phase II trial of nintedanib versus placebo with the neo-adjuvant chemotherapy (NACT) strategy for patients (pts) with advanced unresectable ovarian cancer (OC). Report of the interval debulking surgery (IDS) safety outcome

Background

Improving NACT response rate in pts with OC could lead to increased complete resection rate (CC0) at IDS and better survival. Bevacizumab has been shown to increase response rate to chemotherapy both in first-line (ICON7) and in relapse (OCEANS and AURELIA). Due to concerns about bevacizumab impact on IDS wound healing, the safety and efficacy of nintedanib, an orally available anti-VEGF/PDGFR/FGFR tyrosine kinase inhibitor with a short half-life was explored in the neo-adjuvant setting.

Methods

All patients underwent laparoscopy and their disease was considered as unresectable (impossibility to achieve CC0 at primary surgery). Eligible patients were randomized (2:1) to receive 3 cycles of NACT before IDS and 3 cycles of chemotherapy after IDS with carboplatin + paclitaxel and nintedanib or placebo (at cycle 1&2, 5&6 and at maintenance therapy as single agent during 2 years). The aim of IDS was to achieve CC0. Surgical complications were scored according to Clavien Dindo classification.

Results

A total of 188 patients were included and 121 (64%) patients underwent IDS (49 in placebo arm and 72 in experimental arm). Pts characteristics are well balanced between both arms. No significant difference was observed between the placebo and the nintedanib arm in terms of operating procedure duration (360 vs 330 minutes) and per-operative (18 vs 13%) complications. Bleeding (2 vs 9% of the pts), blood losses (500 vs 675 ml), and transfusion rate (12 vs 26% of the pts) were slightly less frequent in the placebo arm. Around half of the patients experienced at least one postoperative complication: 53% versus 47% in the placebo and nintedanib arm respectively. They were mostly of grade I-II (86% grade I-II, 14% grade III-IVa) with no significant difference between the two arms in type and grade of postoperative complications.

Conclusions

Compare to placebo, the addition of the anti-VEGF nintedanib to neo-adjuvant chemotherapy did not significantly increase the rate of per-operative and post-operative complications of the interval debulking surgery.

Clinical trial identification

NCT01583322

Legal entity responsible for the study

ARCAGY-GINECO

Funding

Boehringer Ingelheim

Disclosure

All authors have declared no conflicts of interest.