Impact of adding nintedanib to neoadjuvant chemotherapy (NACT) for advanced epithelial ovarian cancer (EOC) patients: The CHIVA double-blind randomized phase II GINECO study.

Abstract

5512 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.

CA-125 ELIMination Rate Constant K (KELIM) Is a Marker of Chemosensitivity in Patients with Ovarian Cancer: Results from the Phase II CHIVA Trial

“…In this French multicenter trial, patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC or IV ovarian carcinomas planned to be treated with peri-operative chemotherapy and interval debuking surgery (IDS), were randomly allocated to 1) carboplatin AUC 5-6 and paclitaxel 175mg/m² every 3 weeks combined to nintedanib at 200 mg twice daily, or 2) the same regimen combined to placebo. The enrolled patients received 3-4 cycles before cytoreductive surgery, and then adjuvant 3-4 cycles, followed by a maintenance treatment with nintedanib/placebo for up to 2 years (15). Nintedanib (VARGATEF TM ) is a receptor tyrosine kinase (RTK) inhibitor with potential antiangiogenic and antineoplastic activities (16).…”

“…Nintedanib (VARGATEF TM ) is a receptor tyrosine kinase (RTK) inhibitor with potential antiangiogenic and antineoplastic activities (16). The preliminary outcomes regarding treatment efficacy in CHIVA trial were recently presented (15).…”

An Ontario Health (Cancer Care Ontario) Clinical Practice Guideline: Consolidation or Maintenance Systemic Therapy for Newly Diagnosed Stage II, III, or IV Epithelial Ovary, Fallopian Tube, or Primary Peritoneal Carcinoma

“…There were 12,675 citations from the medical databases search. A total of 27 trials from 40 full-text articles [3, and one additional trial from a conference abstract [16] were then analyzed.…”

“…There were 12,675 citations from the medical databases search. A total of 27 trials from 40 full-text articles [ 3 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ] and one additional trial from a conference abstract [ 16 ] were then analyzed.…”

“…Patients in the nintedanib group had more Grade 3 or 4 adverse effects. In a conference abstract [ 16 ], the additional nintedanib led to worse PFS and worse OS results in patients with stage III or IV ovarian cancer, and increased any Grade 3 or 4 toxicity.…”