1481PD - A phase II study of dovitinib in patients with metastatic or unresectable gastrointestinal stromal tumors after failure of two or more tyrosine kina...

Date 01 October 2012
Event ESMO Congress 2012
Session Sarcoma
Topics Anti-Cancer Agents & Biologic Therapy
GIST
Presenter Yoon-Koo Kang
Authors Y. Kang1, M.H. Ryu2, J.J. Lee3, I. Park4, J.H. Park5, B. Ryoo6
  • 1Dept. Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 138-736 - Seoul/KR
  • 2Division Of Oncology, Dept Of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 138-736 - Seoul/KR
  • 3Department Of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, 138-736 - Seoul/KR
  • 4Oncology, Asan Medical Center, University of Ulsan College of Medicine, 138-736 - Seoul/KR
  • 5Department Of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 138-736 - Seoul/KR
  • 6Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 138-736 - Seoul/KR

Abstract

Objectives

This prospective, phase 2 study evaluated the efficacy and safety of dovitinib in patients (pts) with advanced gastrointestinal stromal tumors (GISTs) who failed previous standard tyrosine kinase inhibitors (TKI).

Methods

Thirty pts with pathologically proven metastatic or unresectable GIST who failed a minimum of both imatinib and sunitinib were accrued between Sep 2011 and Apr 2012. Dovitinib was administered orally at 500 mg qd for 5 consecutive days followed by a 2 day rest period.

Results

The median age was 57.5 years (range, 35-76). All had metastatic disease in the peritoneum (n = 22), liver (n = 20), lung (n = 4), or bone (n = 4). Thirteen pts (43%) also failed nilotinib (n = 8), regorafenib (n = 2) or both nilotinib and regorafenib (n = 3) after failure of imatinib and sunitinib. By RECIST criteria, there were no objective responses, 19 (63.3%) had stable disease (SD), 5 (16.7%) progressive disease (PD), and 6 (20.0%) were not evaluable. By EORTC PET criteria (at 4 weeks), 3 pts (10.0%) achieved a partial response, 15 (50.0%) had SD, 10 (33.3) showed PD, and 2 were not evaluable. With a median follow-up of 4.8 months (range, 0.8-7.5), the medi an progression-free survival (PFS) and overall survival were 3.6 months (95% CI, 2.7-4.4) and 6.2 months (95% CI, 4.9-7.5), respectively. PFS could be predicted by PET response (PD vs no PD) at 4 weeks (p = 0.003). Grade 3 or 4 adverse events of dovitinib with frequency > 5% pts included asthenia (16.7%), leucopenia (6.7%), thrombocytopenia (6.7%), and hypertension (6.7%). Those toxicities were manageable with dose modification, and there were no treatment-related deaths.

Conclusions

Dovitinib showed antitumor activity with manageable toxicities in this heavily pretreated cohort of GIST patients.

Disclosure

Y. Kang: Honoraria, consultant, and research fund from Novartis.

All other authors have declared no conflicts of interest.