Results of the randomized, Placebo (PL)-controlled Phase II study evaluating the efficacy and safety of Regorafenib (REG) in patients (pts) with lo...

Date 30 September 2019
Event ESMO 2019 Congress
Session Proffered Paper - Sarcoma
Topics Bone Sarcomas
Sarcoma
Presenter Florence Duffaud
Citation Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394
Authors F. Duffaud1, J. Blay2, A. Italiano3, E. Bompas4, M. Rios5, N. Penel6, O. Mir7, S. Piperno-Neumann8, C.M. Chevreau9, C. Delcambre10, F. Bertucci11, P. Boudou Rouquette12, H. Vegas13, C. Perrin14, A. Thyss15, C. Schiffler16, L. Monard17, C. Bouvier18, V. Vidal19, S. Chabaud16
  • 1Medical Oncology, CHU La Timone Adultes, 13385 - Marseille/FR
  • 2Medical Oncology, Centre Léon Bérard, 69008 - Lyon/FR
  • 3Medical Oncology, Institute Bergonié, 33076 - Bordeaux/FR
  • 4Medical Oncology, ICO Institut de Cancerologie de l'Ouest René Gauducheau, 44805 - Saint-Herblain/FR
  • 5Medical Oncology, Institut de Cancérologie de Lorraine - Alexis Vautrin, 54519 - Vandoeuvre les Nancy/FR
  • 6General Oncology Department, Centre Oscar Lambret, 59020 - Lille/FR
  • 7Medical Oncology, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 8Medical Oncology, Institut Curie, 75005 - Paris/FR
  • 9Medical Oncology, IUCT-Oncopôle Institut Claudius Regaud, 31059 - Toulouse/FR
  • 10Medical Oncology, Centre Francois Baclesse, 14076 - Caen/FR
  • 11Medical Oncology, Institute Paoli Calmettes, 13274 - Marseille/FR
  • 12Medical Oncology, Hôpital Cochin - APHP, 75014 - Paris/FR
  • 13Medical Oncology, CHRU Bretonneau, 37044 - Tours/FR
  • 14Medical Oncology, Centre Eugene - Marquis, 35042 - Rennes/FR
  • 15Medical Oncology, Centre Antoine Lacassagne, 06189 - Nice/FR
  • 16Biostatistics, Centre Léon Bérard, 69008 - Lyon/FR
  • 17Ucgi, UNICANCER, 75654 - Paris/FR
  • 18Pathologic Anatomy And Cytology, AP-HM CHU NORD, 13015 - Marseille/FR
  • 19Radiology And Medical Imaging, CHU La Timone Adultes, 13005 - Marseille/FR

Abstract

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.

Editorial acknowledgement

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.