NSGO-FANDANGO/ENGOT-EN1: A randomized phase II study of first-line combination chemotherapy with nintedanib/placebo...

Patients with advanced or recurrent endometrial cancer (EC) have poor prognosis despite treatment with combination chemotherapy. This study explored the preliminary efficacy of the potent oral tyrosine kinase inhibitor nintedanib (N), in addition to chemotherapy.

Patients with histologically confirmed stage FIGO 2009 stage IIIC2-IV or recurrent EC were randomized 1:1 to receive N 200 mg or placebo (P), twice daily days 2-21 during chemotherapy (six cycles of Carboplatin (AUC5) and paclitaxel (175 mg/m2) every 21 days (TC)) and in maintenance until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was progression-free survival (PFS).

Between November 30th, 2016, and January 11th, 2019 146 participants (mean age 66.1 years) were randomized and had received at least one dose of N/P: 72 patients to the N + TC arm and 74 to the P + TC arm. After median follow-up time of 43.9 months (95 % CI: 41.8-45.6), median PFS was 8.2 63 months (95 % CI: 5.77-10.27) in the N + TC arm and 7.1 months (95 % CI: 5.40-9.10) in the P + TC arm (HR 0.99, 95 % CI: 0.69-1.43, p = 0.992). There was no difference in median overall survival (OS) (HR 0.82; 96 % CI: 0.54-1.25, p = 0.365). Treatment-emergent grade 3-4 adverse events were higher in N + TC vs P + TC arm, in particular increase in blood alanine aminotransferase (18.1 % vs 4.1 %) and diarrhea (10.8 % and 1.3 %).

Addition of nintedanib to chemotherapy did not improve PFS nor OS. Phase III evaluation of this regimen is not recommended.