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 Anticancer Agents
GIST
Therapy
Biological Therapy
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.