1415P - Long-term safety of regorafenib (REG) in advanced gastrointestinal stromal tumors (GIST): updated safety data of the phase 3 GRID trial

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics GIST
Presenter George Demetri
Citation Annals of Oncology (2016) 27 (6): 483-492. 10.1093/annonc/mdw388
Authors G.D. Demetri1, P. Reichardt2, Y. Kang3, J. Blay4, H. Joensuu5, C. Kappeler6, C. Wuchter-Czerwony7, J. Chung8, A. Wagner9, P.G. Casali10
  • 1Dana-farber Cancer Institute And Ludwig Center, Harvard Medical School, 02215 - Boston/US
  • 2Department Of Hematology, Oncology, And Palliative Medicine, Helios Klinikum Berlin Buch, Berlin/DE
  • 3Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul/KR
  • 4University Claude Bernard, Centre Léon Bérard, Lyon/FR
  • 5Department Of Oncology, Helsinki University Central Hospital, Helsinki/FI
  • 6Clinical Statistics Europe, Bayer Pharma AG, Berlin/DE
  • 7Pharmacovigilance, Bayer Pharma AG, Berlin/DE
  • 8Clinical Development Oncology, Bayer HealthCare Pharmaceuticals, Whippany/US
  • 9Clinical Development Oncology, Bayer Pharma AG, Berlin/DE
  • 10Adult Sarcoma Medical Oncology Unit, Istituto Nazionale Tumori, Milano/IT

Abstract

Background

The GRID trial showed that REG improves progression-free survival (primary endpoint; data cutoff January 2012) versus placebo in patients (pts) with advanced GIST after failure of imatinib and sunitinib (Lancet 2013; 381: 295). At progression, placebo pts could cross over to REG treatment and pts randomized to REG could continue. We present an updated safety analysis of pts in GRID who were treated with REG at any time (any REG; AR) and of the subgroup who had long-term REG (LTR) treatment (>1 year).

Methods

Of the 199 randomized pts (n = 133 REG; n = 66 placebo), 58 placebo pts crossed over to REG. At the time of this analysis (June 2015), a total of 190 pts (95%) were treated with AR and 75 (38%) had LTR. Starting dose was REG 160 mg once daily for the first 3 weeks of each 4-week cycle.

Results

The LTR group tended to have a better ECOG status (PS0: AR 57%/LTR 69%; PS1: AR 43%/LTR 31%). A similar proportion were ≥65 yrs of age (AR 32%; LTR 31%) and treated in the third-line (56%; 61%) or fourth-line and higher settings (44%; 39%). Median (range) treatment duration was 8.8 months (0.02– 48.4) for AR and 22.7 months (12.0 – 48.4) for LTR. Median daily dose was 146.7 mg (AR) and 121.8 mg (LTR). All pts had an NCI-CTCAE (v4.0) treatment-emergent adverse event (TEAE), with the majority occurring in the first months of treatment and significantly lower rates in subsequent months. Most common REG-related grade ≥3 TEAEs included (AR; LTR): hand–foot skin reaction (20.5%; 28.0%); hypertension (24.2%; 34.7%); diarrhea (7.4%; 13.3%); fatigue (4.7%, 4.0%); and oral mucositis (2.1%, 2.7%). Although rates of treatment modifications due to REG-related TEAEs were higher in the LTR group (66.8% AR; 82.7% LTR), discontinuation rates due to REG-related TEAEs were similar (8.9% AR; 10.7% LTR), with the majority of events leading to discontinuation reported only once. There were no additional REG-related deaths since the primary analysis.

Conclusions

Patients who had LTR tended to have a better ECOG status. The updated safety profile of GIST pts treated with REG in GRID is consistent with the profile reported at primary study completion. For pts treated with REG >1 year, no unexpected safety findings were observed.

Clinical trial identification

NCT01271712

Legal entity responsible for the study

Bayer

Funding

Bayer

Disclosure

G.D. Demetri: Stock ownership: Kolltan Pharmaceuticals, Blueprint Medicines, G1 Therapeutics, Caris, Champions Oncology, Bessor Pharmaceuticals. Advisory board: Bayer, Novartis, Pfizer, Lilly, EMD-Serono, Sanofi Oncology, Janssen Oncology, GlaxoSmithKline, Daiichi-Sankyo, Ariad, AstraZeneca, WIRB Copernicus Group, ZioPharm, Polaris Pharmaceuticals, Kolltan Pharmaceuticals, Blueprint Medicines, G1 Therapeutics, Caris, Champions Oncology, Bessor Pharmaceuticals. Board of directors: Blueprint Medicines Board of Directors. Corporate-sponsored research: Bayer, Novartis, Pfizer, EMO-Serono, Sanofi Oncology, Janssen Oncology, Glaxo-Smith-Kline (all to Dana-Farber). P. Reichardt: Advisory board: Amgen; ARIAD; Bayer; GlaxoSmithKline; Novartis; Pfizer; PharmaMar Corporate sponsored research: Novartis. Y-K. Kang, J-Y. Blay: Advisory board: Bayer, Novartis. H. Joensuu: Stock ownership: Orion Pharma Advisory board: Blueprint Medicines, Ariad. C. Kappeler, A. Wagner: Other substantive relationships: Bayer (employment). C. Wuchter-Czerwony, J. Chung: Other substantive relationships: Bayer employment. P.G. Casali: Advisory board: Amgen Dompé, ARIAD, Bayer, Blueprint Medicines, Eisai, GSK, Lilly, Merck SD, Merck Serono, Novartis, Pfizer, PharmaMar Corporate-sponsored research: Amgen Dompé, Bayer, Eisai, GSK SK, Novartis, Pfizer, PharmaMar (all institution).