1478O - Clinical benefit with regorafenib across subgroups and post-progression in patients with advanced gastrointestinal stromal tumor (GIST) after progre...

Date 30 September 2012
Event ESMO Congress 2012
Session Sarcoma
Topics Cytotoxic agents
Biological therapy
Presenter Peter Reichardt
Authors P.G. Casali1, P. Reichardt2, Y. Kang3, J. Blay4, P. Rutkowski5, H. Gelderblom6, P. Hohenberger7, I. Kuss8, D. Laurent8, G.D. Demetri9
  • 1Struttura Semplice Trattamento Medico Dei Sarcomi Dell'adulto, Istituto Nazionale Tumori, 20133 - Milano/IT
  • 2Interdisciplinary Oncology, HELIOS Klinikum Bad Saarow, DE-15526 - Bad Saarow/DE
  • 3Dept. Of Oncology, Asan Medical Center, KR-138-736 - Seoul/KR
  • 4Medical Oncology, Centre Léon Bérard, 69373 - Lyon CEDEX/FR
  • 5Centrum Onkologii-, Instytut im. Marii Sklodowskiej – Curie, 02-781 - Warszawa/PL
  • 6Medical Oncology, Leiden University Medical Center, 2333 ZA - Leiden/NL
  • 7Dept. Of Surgery, UniversitaetsMedizin Mannheim, 68167 - Mannheim/DE
  • 8Global Clinical Development Oncology 2, Bayer HealthCare Pharmaceuticals, 13353 - Berlin/DE
  • 9Ludwig Center At Dana-farber/harvard Cancer Center And Sarcoma Center, Dana-Farber Cancer Institute, 02215 - Boston/US




Regorafenib (REG) therapy significantly improved progression-free survival (PFS) in patients (pts) with GIST after failure of both IM and SU (J Clin Oncol 2012; 30: suppl; abstr LBA10008). Results of subgroup and post-progression analyses are presented here.


Pts were randomized (2:1) to receive best supportive care plus either REG 160 mg or placebo (PL) po once daily (3 wks on/1 wk off). The primary endpoint was PFS. Upon progression in either arm, unblinding could occur. Pts on PL were eligible for crossover to open-label (OL) REG and progressive pts on REG were allowed to continue REG upon local physician's choice.


GRID screened 234 pts and randomized 199 (REG: 133, PL: 66), well balanced for baseline characteristics. The PFS primary endpoint (according to RECIST) was met both per central review (median PFS 4.8 mo for REG vs. 0.9 mo for PL), and by investigator assessment (median PFS 7.4 mo for REG vs. 1.7 mo for PL). Exploratory sensitivity analyses demonstrate similar positive impact on PFS across pre-specified subgroups by number of prior systemic therapy, geographical region, age, baseline ECOG score, duration of prior treatment with imatinib, or KIT/PDGFRA mutation. Median overall survival has not been reached in either arm. Taking the double-blind and OL periods together, 188 pts received REG. Post-progression PFS per investigator assessment was 5.0 mo for pts in the PL arm who crossed over to REG (n = 56), and 4.5 mo for pts in the REG arm who continued to receive REG after unblinding (n = 41).


REG induced significant PFS benefit in GIST pts following resistance to both IM and SU across all pre-specified subgroups. Interestingly, 41 pts on REG (out of 133) whose physicians decided to continue REG after RECIST progression had an additional PFS benefit which was in the same range. This suggests that continuous kinase inhibition after progression may benefit pts by slowing tumor progression and/or that RECIST criteria for progression applied by blind central review have clinical shortcomings.


P.G. Casali: Consultant/advisory: Bayer, MSD, GSK, Infinity, Novartis, Pfizer, PharmaMar, Sanofi Honoraria: Novartis, Pfizer, PharmaMar Research funds: Amgen Dompe, Bayer, MSD, GSK, Imclone, Infinity, Lilly, Molmed, Novartis, Pfizer, PharmaMar, Sanofi.

P. Reichardt: Consultant/advisory: Bayer.

Y. Kang: Consultant/advisory: Bayer Research funding: Bayer.

J. Blay: Honoraria: Pharmama, Novartis, Pfizer, Roche, GSK Research funding: Pharmama, Novartis, Pfizer, Roche, GSK.

P. Rutkowski: Consultant/advisory: Novartis, MSD, BMS Honoraria: Novartis, Pfizer, BMS, MSD, Roche.

M. Leahy: Research funding as PI for GRID study at Christie Hospital, Manchester, UK.

M. von Mehren Consultant/advisory: Novartis, Pfizer, Astex; Honoraria: Novartis, Pfizer.

H. Joensuu Consultant/advisory: Novartis, Boehringer-Ingelheim.

A. Le Cesne Honoraria: Novartis, Pfizer, Pharmamar.

P. Schöffski: Research funding: Bayer.

R. Maki: Consultant/advisory: Bayer, Pfizer, Novartis; Honoraria: Bayer, Pfizer, Novartis; Research funding: Pfizer; Expert testimony: Pfizer.

I. Kuss: Employment: Bayer.

D. Laurent: Employment: Bayer Stock ownership: Bayer.

G.D. Demetri: Consultant/advisory: Novartis, Pfizer, GSK, Roche, Deciphra (uncompensated), Infinity Research funding: Novartis, Pfizer, GSK, Infinity Expert testimony (uncompensated): Infinity, Pfizer, Novartis, Bayer.

All other authors have declared no conflicts of interest.