Results of the randomized, placebo (PL)-controlled phase II study evaluating the efficacy and safety of regorafenib (REG) in patients (pts) with locally advanced (LA) or metastatic relapsed chondrosarcoma (CS), on behalf of the French Sarcoma Group (FSG) and UNICANCER

Background REGOBONE, a non-comparative phase II, double-blind, PL-controlled trial was designed to evaluate the activity of REG, an oral multikinase inhibitor, in four parallel independent bone sarcomas cohorts: osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma. REG demonstrated promising activity in the osteosarcoma cohort (Lancet Oncol 2019). We report here the CS cohort results. Methods Eligible CS pts were randomized (2:1) to receive either REG (160 mg/d, 21/28 d) or PL with optional cross-over at the time of centrally confirmed progressive disease (PD). Key-eligibility criteria were age ≥10 years, histologically confirmed diagnosis of CS, confirmed measurable PD not amenable to curative-intent, 1-2 previous chemotherapy (CT) regimen(s) for relapsed disease, ECOG 0-1. 24 pts were planned in the REG arm based on a A’Hern’s single-stage design for phase II trials (1-sided a = 0.05, and 80% power) to detect a 25% improvement in the progression-free rate (PFR) at 12 weeks (P0=50%) as evaluated by central review per RECIST1.1. Major secondary endpoints were PFS, OS and safety. Results From September 2014 to February 2019, 46 CS pts were included. Six pts were not eligible for efficacy analysis. Of 40 efficacy-evaluable pts (16 in PL arm and 24 in REG arm); 25 were men, median age was 61 (20-75) years. 13 pts (54.2%; one-sided CI95% = [35.8-[) were non-progressive at 12 weeks in the REG arm vs. 6 (37.5%; CI95% = [17.8-[) in the PL arm. Median PFS was 19.4 (CI95% = 11.4-35) vs. 8 (CI95%= 4.3-23.4) weeks for REG and PL arms, respectively. At the time of the analysis there is not enough event to describe OS. 14 pts crossed-over to REG after PD on PL. The most common Gr3-5 REG-related AEs during the double-blind period were hypertension (12%), cutaneous toxicity (8%), asthenia (8%), diarrhea (8%), thrombocytopenia (8%), and 1 fatal liver cytolysis. Conclusions Despite a PFR at 12 weeks lower than expected, this randomized non comparative study shows a promising signal of benefit of REG in relapsed CS, with a median of PFS of 19 weeks and, an acceptable toxicity. Clinical trial identification EudraCT: 2013-003910-42, NCT02389244. Legal entity responsible for the study UNICANCER. Funding Bayer HealthCare SAS. Disclosure F. Duffaud: Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Roche; Advisory / Consultancy: Lilly; Travel / Accommodation / Expenses: Pharmamar; Travel / Accommodation / Expenses: Leo Pharma. J. Blay: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Bayer; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): GSK. O. Mir: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Bayer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Blueprint Medicines; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Eli-Lilly; Honoraria (self), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Incyte; Honoraria (self), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Lundbeck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Servier; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Vifor Pharma. P. Boudou Rouquette: Honoraria (self): BMS; Honoraria (self): Roche; Travel / Accommodation / Expenses: Pharmamar; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Novartis. All other authors have declared no conflicts of interest.