Regorafenib treatment for advanced, refractory gastrointestinal stromal tumor: a report of the UK managed access program

Attila Kollàr; Marco Maruzzo; Christina Messiou; Elisabeth Cartwright; Aisha Miah; Juan Martin-Liberal; Khin Thway; Ellen McGrath; Alison Dunlop; Komel Khabra; Beatrice Seddon; Palma Dileo; Mark Linch; Ian Judson; Charlotte Benson

doi:10.1186/2045-3329-4-17

Regorafenib treatment for advanced, refractory gastrointestinal stromal tumor: a report of the UK managed access program

Clin Sarcoma Res. 2014 Dec 4:4:17. doi: 10.1186/2045-3329-4-17. eCollection 2014.

Authors

Affiliations

¹ Department of Medical Oncology, University Hospital Bern, Inselspital, 3010 Bern, Switzerland.
² Sarcoma Unit, Royal Marsden NHS Foundation Trust, Fulham Road, SW3 6JJ London, UK.
³ Research Data Management and Statistics Unit (RDSU), The Royal Marsden NHS Foundation Trust, London, UK.
⁴ University College London Hospitals NHS Foundation Trust, Euston Road, NW1 2BU London, UK.

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.

Keywords: Choi; Gastrointestinal stromal tumor; Mutation; Regorafenib.