199 Randomised Phase II BGOG/ENGOT-cx1 study of paclitaxel-carboplatin with or without nintedanib in first-line recurrent or advanced cervical cancer

Introduction/Background* Platinum in combination with paclitaxel (P) and bevacizumab is the standard of care in first-line recurrent/advanced cervical cancer (Tewari, NEJM 2020). Nintedanib is an oral tyrosine kinase inhibitor targeting, among others, vascular endothelial growth factor receptor. Methodology Double-blind phase II randomised study in patients with first-line recurrent or primary advanced (FIGO stage IVB) cervical cancer. Patients received carboplatin AUC 5-6 and paclitaxel 175mg/m2 q 3 weeks with oral nintedanib 200 mg BID/placebo. Stratification factor was primary advanced versus recurrent disease. The primary endpoint was progression-free survival (PFS) at 1,5 years with at least 87 events and α=0.15, β=80%, one sided, in favor of the nintedanib (N) versus control (C) arm. The study (NCT02009579) was performed according to the ENGOT model A. Result(s)* 120 patients (62 N, 58 C) were randomised between March 2014 and October 2018. Median follow-up was 35 months. Baseline characteristics were similar in both groups (total population: squamous cell carcinoma 62%, prior radiotherapy 64%, primary advanced 25%, recurrent 75%). The primary endpoint was met with a PFS at 1.5 years of 15.1% versus 12.8% in favour of the nintedanib arm (p = 0.057). Median overall survival (OS) was 21.7 and 16.4 months for N and C, respectively. Subgroup analysis did not demonstrate a difference in PFS in the primary advanced setting, but in the recurrent setting the 1 year PFS was 22.8% and 14.9% for N and C, respectively. Confirmed RECIST response rate was 48% for N and 39% for C. No new adverse events were noted for N. However N was associated with numerically more serious adverse events for anemia and febrile neutropenia. Discontinuation of chemotherapy was similar in both groups. N was discontinued in 3% versus placebo in 1.6% of the patients. Dose reduction of N was necessary in 53% of the patients. Conclusion* The study met its primary endpoint with a prolonged PFS in the N arm. No new safety signals were observed.