Background: Nintedanib, an oral inhibitor of VEGF-FGF-PDGF receptors, has been shown to prolong progression-free survival (PFS) when added to adjuvant chemotherapy after primary surgery (duBois A, Lancet Oncol 2015). CHIVA trial explored the role of nintedanib in combination with NACT. Methods: Patients (pts) with FIGO stage IIIC-IV chemotherapy-naive AEOC considered as unresectable after laparoscopic evaluation were randomized (2:1) to be treated with 3 to 4 cycles (cy) of carboplatin (AUC 5 mg/mL/min) and paclitaxel (175 mg/m²) (CP) before interval debulking surgery (IDS) followed by 2 to 3 cy of CP for a total of 6 cy, plus either 200 mg of Nin (armA) or placebo (armB) twice daily on days 2–21 q3week at cy 1&2, 5&6 and maintenance therapy for up to 2 years. The primary endpoint was PFS. Results: Between Jan. 2013 and May 2015, 188 pts were included (124 arm A, 64 arm B) with a median Peritoneal Cancer Index of 22 (range 19-27). Pts characteristics were well balanced between both arms. Median PFS was 14.4 mos (95%CI 12.2-15.4) and 16.8 (13.3-21.4) in arm A and B respectively (HR:1.50, p=0.02). Median OS was 37.7 mos (29.8-41.0) and 44.1 (32.7-not reached) in arm A and B respectively (HR:1.54, p=0.053). Arm A was associated with more toxicity compared to arm B respectively (Grade 3&4 adverse events: 92 versus 71%), with increased early treatment discontinuation before the 3rd cy (14.5 vs 6.2%) & CP dose reduction (12% vs 0%). Pts in Arm A reported inferior RECIST ORR to pre-IDS therapy compared to Arm B (35.1 vs 55.9%). IDS was performed significantly less frequently in arm A (58.1%) vs arm B (76.6%). However among pts who underwent IDS, complete surgical cytoreduction rate (76%) and peri/postoperative complication rate (11.2%) were similar in both arms. Conclusions: The addition of nintedanib to NACT increases toxicity and compromise chemotherapy efficacy leading to a reduced rate of IDS and worse PFS and OS for advanced EOC patient. Clinical trial information: 2011-006288-23.