Abstract 1919P
Background
Patients with progressive advanced medullary thyroid cancer (MTC) after vandetanib and/or cabozantinib had limited treatment options at the time the trial was launched. Nintedanib is a triple angiogenesis inhibitor. The aim of this prospective randomized double-blind phase II study was to evaluate nintedanib in progressing MTC pts after 1 or 2 lines of prior TKI treatment.
Methods
Pts with documented RECIST v1.1 progression on a prior TKI treatment were randomized to nintedanib or placebo (2:1 ratio). The primary endpoint was progression free survival (PFS) using local RECIST v1.1. With a 1-sided alpha 10%, the study was powered at 90% level to detect a Hazard Ratio (HR) of 0.6 in PFS. The cohort was stopped due to slow accrual with 32/67 pts enrolled without reaching the targeted statistical power. Treatment effects were estimated using the Cox model and presented with their 95% confidence interval (CI) without p-values.
Results
Thirty-two pts patients (med age: 56.9 yrs; 75% male), with progressing MTC were enrolled; 31 were randomized to receive nintedanib (22 pts) or placebo (9 pts) (intention to treat); 20 pts (15 nintedanib; 5 placebo met all inclusion criteria (per protocol)). In the per-protocol population, median PFS was 3.9 (3.0, 7.1) months under placebo and 7.0 (1.8, 8.8) months under nintedanib (HR=0.49; 95% CI 0.16-1.53). The best overall response was stable disease in 9 (60%) pts under nintedanib and 4 (80%) under placebo. Median overall survival was 12.3 months under nintedanib (median follow-up 48.4 months) and 16.4 months under placebo (median follow-up 19.7 months). In the intention to treat population, median PFS was 3.6 (1.8, 5.5) months under placebo and 6.4 (1.9, 8.7) months under nintedanib (HR=0.40; 95% CI: 0.17-0.99) At least one Grade 3-4 adverse event occurred in 13 (59%) pts under nintedanib and 3 (33%) under placebo. The most common AEs under nintedanib were diarrhea (18 %), nausea (9%) increase in gammaGT (18%) and lymphopenia (18%).
Conclusions
Due to a slow accrual the study was closed. Among pts included, nintedanib appears safe, yet no conclusion on efficacy could be drawn due to the low power of the study.
Clinical trial identification
NCT01788982.
Editorial acknowledgement
Legal entity responsible for the study
EORTC.
Funding
Boehringer Ingelheim.
Disclosure
K. Newbold: Honoraria (self): Eisai. P. Schoeffski: Honoraria (self), Advisory/Consultancy: Deciphera; Honoraria (self), Advisory/Consultancy: Blueprint Medicines; Honoraria (self), Travel/Accommodation/Expenses: Boehringer Ingelheim; Advisory/Consultancy: Plexxikon; Advisory/Consultancy, Research grant/Funding (institution): Eisai; Advisory/Consultancy: Loxo; Advisory/Consultancy: Lilly; Advisory/Consultancy: Ellipses Pharma; Advisory/Consultancy: Merck; Advisory/Consultancy: Servier; Advisory/Consultancy: Genmab; Advisory/Consultancy: Adaptimmune; Advisory/Consultancy: Intellisphere; Advisory/Consultancy: Transgene; Advisory/Consultancy: Exelixis; Research grant/Funding (institution): CoBioRes NV; Research grant/Funding (institution): G1 Therapeutics; Research grant/Funding (institution): PharmaMar; Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Ipsen. L.D. Locati: Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self): MSD; Honoraria (self), Advisory/Consultancy: Merck Serono; Honoraria (self): Mc Cann Healthcare; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Biogen. C. de la Fouchardiere: Advisory/Consultancy, Travel/Accommodation/Expenses: Servier; Advisory/Consultancy: Bayer; Advisory/Consultancy: Lilly; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Pierre Fabre Oncology; Advisory/Consultancy: MSD; Advisory/Consultancy, Travel/Accommodation/Expenses: Eisai; Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: BMS. L. Bastholt: Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Sanofi-Genzyme; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Speaker Bureau/Expert testimony: Roche; Honoraria (self), Speaker Bureau/Expert testimony: Merck MSD. E. Kapiteijn: Honoraria (institution): Eisai; Honoraria (institution): Bayer; Honoraria (institution): Sanofi Genzyme. S. Leboulleux: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Eisai; Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Research grant/Funding (institution): Sanofi Genzyme; Research grant/Funding (institution): Novartis. All other authors have declared no conflicts of interest.