705P - Phase I trial of sunitinib plus imatinib in patients with metastatic or unresectable gastrointestinal stromal tumors (GIST)

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Anti-Cancer Agents & Biologic Therapy
GIST
Presenter Antonio Lopez Pousa
Authors A. Lopez Pousa1, L. Paz-Ares2, C. Pericay3, X. Garcia Del Muro4, M.J. Flor5
  • 1Medical Oncology, Hospital de la Sta. Creu i St. Pau, 08025 - Barcelona/ES
  • 2Hospital Virgen del Roc, 41020 - Seville/ES
  • 3Medical Oncology, Corporació Sanitària Parc Taulí Institut Universitari, 08208 - Sabadell/ES
  • 4Medical Oncology, Institut Catala d'oncologia, ES-08907 - L'Hospitalet de Llobregat/ES
  • 5Oncology Service, Hospital Virgen del Rocio, 41020 - Seville/ES

Abstract

Background

Patients (Pts) with GIST harboring mutations in KIT exon 9 or wild type tumors showed better responses to sunitinib along with longer median progression-free survival (PFS) rates compared with exon 11 mutant tumors pts. We have hypothesized that the combination of S plus I in unresectable GIST would be synergistic and associated to a tolerable side effect profile.

Methods

This is a phase I, dose-escalation study to determine the maximum-tolerated dose (MTD), safety and antitumor activity measured by response rate of S plus I in naive patients with metastatic or unresectable GIST. Pts with adequate organ function, performance status (ECOG) 0-1, age >18 years, were eligible. Treatment consisted on oral S 25mg/day d1-28 combined with oral I 300mg/day d1-28 (level I) or oral I 400mg/day d1-28 (level II).

Results

3 pts were enrolled on Level I. No DLTs were observed. At level II 7 pts were enrolled and 1 DLT was observed (posterior reversible encephalopathy syndrome on day19). Although 1DLT was observed in 7 pts, decision was not to increase the S dose to 37.5 mg due to toxicity. Other non-DLTs adverse events were G4 hyperbilirubinemia in cycle 2 and G4 intratumoral haemorrhage in cycle 3. The MTD was determined as I 400mg/day and S 25mg/day. Other toxicities were neutropenia, diarrhoea, vomiting, asthenia, musculoskeletal pain, anaemia and bacteraemia. Median time on treatment with the combination was 16 weeks (range 12-152) on level I and 20 weeks (range 3-88) on level II. 66% of patients completed 20 weeks of treatment. Serious Adverse Events were reported in 4 pts; 3 deaths were reported, one due to disease progression, another due to reversible encephalopathy syndrome and the last one due to septic shock. A partial response was achieved in 6 (60%) pts; complete response in 2 (1 wild-type) (20%) and stable disease in 1 (10%).

Conclusions

Sunitinib 25mg/day plus Imatinib 400mg/day is the MTD and a safe and well tolerated combination in pts with metastatic or unresectable GIST. Response rates seems to be higher than those expected and previously observed with S or I monotherapy.

This study was supported by an Independent Investigator Research grant from Pfizer, Inc

Disclosure

All authors have declared no conflicts of interest.