1430P - Identifying biological and clinical characteristics of patients with gastrointestinal stromal tumours (GIST) responding to imatinib therapy for mor...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Biomarkers
GIST
Pathology/Molecular Biology
Presenter Jacob Bosma
Citation Annals of Oncology (2014) 25 (suppl_4): iv494-iv510. 10.1093/annonc/mdu354
Authors J. Bosma1, M. Verboom2, I. Gataa3, E.V. Werkhoven4, H. Gelderblom5, R. Mathijssen6, A. Reyners7, C. Osuch8, J.A. Siedlecki9, K. Kubackova10, I. Kocakova10, E. Bylina11, A. Le Cesne3, P. Rutkowski11, N. Steeghs1
  • 1Dpt Of Medical Oncology, The Netherlands Cancer Institute / Antoni van Leeuwenhoek, 1006 BE - Amsterdam/NL
  • 2Dpt Of Medical Oncology, Leiden University Medical Center (LUMC), Leiden/NL
  • 3Medical Oncology, Institut de Canc, FR-94805 - Villejuif CEDEX/FR
  • 4Dpt Of Biostatistics, The Netherlands Cancer Institute / Antoni van Leeuwenhoek, 1006 BE - Amsterdam/NL
  • 5Medical Oncology, Leiden University Medical Center (LUMC), 2333ZA - Leiden/NL
  • 6Department Of Medical Oncology, Erasmus University Medical Center, Rotterdam/NL
  • 7Medical Oncology, University Medical Center Groningen, 9700 RB - Groningen/NL
  • 8Surgical Oncology, Iagiellonian University Cracow, Cracow/PL
  • 9Dept Of Molecular Biology, MSC Memorial Cancer Centre and Institute Maria Sklodowska-Curie, 02-781 - Warsaw/PL
  • 10Oncology And Radiotherapy, Fakultni Nemocnice V Motole, Praha/CZ
  • 11Soft Tissue/bone Sarcoma And Melanoma, MSC Memorial Cancer Centre and Institute Maria Sklodowska-Curie, 02-781 - Warsaw/PL

Abstract

Aim

Since 2002 imatinib mesylate (IM) is registered for patients with advanced irresectable/metastatic GIST. A subset of patients has a (very) long-term response to IM therapy.

Methods

Clinical data were retrospectively collected from 4 international databases (Poland, France, Czech Republic, the Netherlands). Eligible patients had advanced GIST and started with IM between November 2000 and January 2009. We assessed biological and clinical factors associated with the duration of IM treatment and overall survival (OS).

Results

A total of 643 patients were identified with a median follow-up of 7.9 years, of whom 24 were still on IM at last follow-up. Median OS was 7 years (95% CI 6.1-7.7), median IM treatment time was 35 months (95% CI 31-41), with 226 and 40 patients being treated for more than 5 and 10 years, respectively. Factors associated with a response duration >5 years, tested by univariate analysis, were complete surgical resection of the primary tumour (p<0.05), good WHO performance status (PS 0) (p<0.0001), KIT exon 11 mutation (p<0.05) and normal baseline haemoglobin (p<0.05), leukocytes (p<0.05), neutrophils (p<0.05) and albumin levels (p<0.0001). Patients with local recurrence or metastases in the liver only were on IM for a longer period compared to patients with peritoneal metastases (p<0.05). No additional factors could be identified in the (small) cohort of patients responding more then 10 years. Remarkably, in our analysis no statistically significant influence of the primary tumour size, location of the primary tumour and mitotic index (at the time of diagnosis) on both overall survival and duration of IM treatment could be demonstrated.

Conclusions

GIST patients with a complete resection of the primary tumour, good WHO performance status, KIT exon 11 mutation and normal haemoglobin, leukocytes, neutrophils and albumin levels at baseline are more likely to respond to IM therapy for a longer period. Since data on patients responding over 10 years remain limited, a case-control study will be initiated to further elucidate factors influencing very long term responses.

Disclosure

H. Gelderblom: research grants from Novartis en Pfizer; A. Le Cesne: Honoraria : Novartis, Pfizer, Pharmamar, GSK for advisory boards; P. Rutkowski: honoraria and Advisory Board for Novartis, Advisory Board for Bayer, travle grants from Pfizer; N. Steeghs: Grants for Netherlands GIST registry (Novartis, Pfizer en Bayer). All other authors have declared no conflicts of interest.