title: Regorafenib treatment for advanced, refractory gastrointestinal stromal tumor: a report of the UK managed access program.
abstract: BACKGROUND
  Tyrosine kinase inhibitors (TKI) have revolutionized the treatment of gastrointestinal stromal tumors (GIST) although most patients develop resistance to first and second-line therapies. Regorafenib, an oral multi-targeted TKI, has demonstrated benefit in previously treated GIST patients.
  
  
  METHODS
  We assessed safety and activity of regorafenib in patients treated within the Managed Access Program (MAP). All consecutive patients with advanced GIST who had progressed on or were intolerant to imatinib and sunitinib were recruited from the Royal Marsden and University College Hospitals. We retrospectively reviewed the data for response, toxicity, treatment duration and survival. Response was assessed by RECIST and Choi criteria. Toxicity was graded according to CTCAE v4.0 criteria.
  
  
  RESULTS
  20 patients were included in the MAP in the UK between 3/2013 and 9/2013. Median age was 68 (range 45-87), 65% of patients were male. Performance Status was 0-1 for 18 patients (90%), 2 for 2 patients (10%). The median treatment duration was 9.25 months (range 0.1-15.33). 18 patients were assessable for response and all patients attained a best response of at least stable disease. At a median follow-up of 12.6 months, there were 2 partial responses (11%) by RECIST and 7 partial responses (39%) according to Choi criteria. 7 patients remain on regorafenib. 3 patients discontinued treatment due to unacceptable adverse events; fistulation, myalgia and fatigue. 10 (50%) patients had grade 3 toxicities and 11 (55%) patients required a dose reduction. Median PFS was 9.4 months (95% Cl: 6.2-not calculable) and median OS was 12.2 months (95% Cl: 10.5-not calculable). Notably, prolonged stable disease was seen in 1 patient with exon 9 mutation and 1 patient with PDGFR D842V mutation.
  
  
  CONCLUSIONS
  These data demonstrate encouraging activity and tolerability of regorafenib in routine clinical practice. The documented adverse events are in line with previous trial data.
authors.affiliation: Department of Medical Oncology, University Hospital Bern, Inselspital, 3010 Bern, Switzerland.
authors.forename: Attila
authors.initials: A
authors.lastname: Kollàr
authors.affiliation: Sarcoma Unit, Royal Marsden NHS Foundation Trust, Fulham Road, SW3 6JJ London, UK.
authors.forename: Marco
authors.initials: M
authors.lastname: Maruzzo
authors.affiliation: Sarcoma Unit, Royal Marsden NHS Foundation Trust, Fulham Road, SW3 6JJ London, UK.
authors.forename: Christina
authors.initials: C
authors.lastname: Messiou
authors.affiliation: Sarcoma Unit, Royal Marsden NHS Foundation Trust, Fulham Road, SW3 6JJ London, UK.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Cartwright
authors.affiliation: Sarcoma Unit, Royal Marsden NHS Foundation Trust, Fulham Road, SW3 6JJ London, UK.
authors.forename: Aisha
authors.initials: A
authors.lastname: Miah
authors.affiliation: Sarcoma Unit, Royal Marsden NHS Foundation Trust, Fulham Road, SW3 6JJ London, UK.
authors.forename: Juan
authors.initials: J
authors.lastname: Martin-Liberal
authors.affiliation: Sarcoma Unit, Royal Marsden NHS Foundation Trust, Fulham Road, SW3 6JJ London, UK.
authors.forename: Khin
authors.initials: K
authors.lastname: Thway
authors.affiliation: Sarcoma Unit, Royal Marsden NHS Foundation Trust, Fulham Road, SW3 6JJ London, UK.
authors.forename: Ellen
authors.initials: E
authors.lastname: McGrath
authors.affiliation: Sarcoma Unit, Royal Marsden NHS Foundation Trust, Fulham Road, SW3 6JJ London, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Dunlop
authors.affiliation: Research Data Management and Statistics Unit (RDSU), The Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Komel
authors.initials: K
authors.lastname: Khabra
authors.affiliation: University College London Hospitals NHS Foundation Trust, Euston Road, NW1 2BU London, UK.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Seddon
authors.affiliation: University College London Hospitals NHS Foundation Trust, Euston Road, NW1 2BU London, UK.
authors.forename: Palma
authors.initials: P
authors.lastname: Dileo
authors.affiliation: University College London Hospitals NHS Foundation Trust, Euston Road, NW1 2BU London, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Linch
authors.affiliation: Sarcoma Unit, Royal Marsden NHS Foundation Trust, Fulham Road, SW3 6JJ London, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Judson
authors.affiliation: Sarcoma Unit, Royal Marsden NHS Foundation Trust, Fulham Road, SW3 6JJ London, UK.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Benson
keywords: Choi; Gastrointestinal stromal tumor; Mutation; Regorafenib