Adjuvant GIST/EORTC 62024

Protocol Title

Intermediate and high-risk localised, completely resected, gastro-intestinal stromal tumours (GIST) expressing c-kit receptor: A controlled randomised trial on adjuvant imatinib mesylate (Glivec ®) versus no further therapy after completing surgery.

Publication Reference

Casali PG, Le Cesne A, Poveda Velasco A, Kotasek D, Rutkowski P, Hohenberger P, Fumagalli E, Judson IR, Italiano A, Gelderblom H, Adenis A, Hartmann JT, Duffaud F, Goldstein D, Broto JM, Gronchi A, Dei Tos AP, Marréaud S, van der Graaf WTA, Zalcberg JR, Litière S, Blay J-Y. Time to definitive failure to the first tyrosine kinase inhibitor in localized GI stromal tumors treated with imatinib as an adjuvant: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group intergroup randomized trial in collaboration with the Australasian Gastro-Intestinal Trials Group, UNICANCER, French Sarcoma Group, Italian Sarcoma Group, and Spanish Group for Research on Sarcomas. Journal of Clinical Oncology 2015; 33(36): 4276–4283

Conference Presentations Reference

1. Casali P, LeCesne A, Valasco A, Kotasek D, Rutkowski P, Hohenberger P, Fumagalli E, Judson I, Italiano A, Broto J, Gronchi A, Dei Tos A, Marreaud S, Van Der Graaf W, Zalcberg J, Litière S, Blay J, EORTC Soft Tissue and Bone Sarcoma Group (EORTC STBSG), French Sarcoma Group (FSG), Italian Sarcoma Group (ISG), Grupo Español de Investigación en Sarcomas (GEIS), Australasian Gastro-Intestinal Trials Group (AGITG). Imatinib failure-free survival in patients with localized gastrointestinal stromal tumors treated with adjuvant imatinib: the EORTC/AGITG/FSG/GEIS/ISG randomized controlled phase III trial. American Society of Clinical Oncology Annual Meeting; 31 May–4 Jun 2013; Chicago. Journal of Clinical Oncology; 31 (suppl.): 10500.
2. Hohenberger P, Rutkowski P, Bonvalot S, van Coevorden F, Stoeckle E, Olungu C, Ouali M, Casali P, Gronchi A. Analysis of the quality of reporting surgical procedures in patients undergoing resection for primary gastrointestinal stromal tumors: a reporting tool derived from the EORTC–STBSG 62024 trial. American Society of Clinical Oncology Annual Meeting; 31 May–4 Jun 2013; Chicago.
3. Van Glabbeke MM. Owzar K, Rankin C, Simes J, Crowley J; GIST Meta-analysis Group (MetaGIST). Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors: a meta-analyis based on 1640 patients. 43rd Annual Meeting of the American Society of Clinical Oncology; 1–5 Jun 2007; Chicago. Journal of Clinical Oncology 2007; 25 (18S, Part 1): 10004.

Aim

The overall aim of the Adjuvant GIST trial was to assess whether imatinib, as an adjunct to complete surgery, could improve the prognosis of patients with intermediate and high-risk, localised gastrointestinal stromal tumours (GIST).

The original primary objective of the trial was to compare overall survival between the treatment and observation groups. The primary objective was changed to imatinib monotherapy failure-free survival, based on recommendations by the study Independent Data Monitoring Committee, because of improvements in the prognosis of advanced GIST patients. The secondary objectives were to compare relapse-free survival and relapse-free interval between the treatment and observation groups, and to assess the safety of imatinib given as an adjunct to complete surgery.

Background

Gastrointestinal stromal tumours are rare cancers that are highly resistant to standard therapies, including surgery, chemotherapy and radiation. When the cancer has metastasised, it cannot be surgically removed and is not curable with any current treatment.

Although Imatinib has been shown to be highly effective in prolonging survival in patients with advanced cancer, the drug’s potential has yet to be explored as adjuvant treatment after surgery. In addition, the long term effect of this drug has yet to be investigated.

The aim of the Adjuvant GIST trial (also known as EORTC 62024) is to assess the impact of Imatinib as additional treatment to complete surgery to see if it could improve the prognosis of patients with intermediate to high risk localised gastrointestinal stromal tumours. The study would monitor patients who were given Imatinib tablets versus patients who only received standard treatment with no drugs over a period of 2 years.

After two years of treatment and a median follow up of 4.7 years, interim analysis of the data confirmed that adjuvant imatinib improved relapse-free survival compared to no adjuvant therapy. No significant difference in imatinib monotherapy failure-free survival was observed, although there was a trend in favour of adjuvant imatinib in the high-risk subgroup.

The trial is now in the follow up stage and the final analysis will be conducted. Results of the interim analysis were published in the Journal of Clinical Oncology in October, 2015.

Clinical Trial Design

The adjuvant GIST/EORTC 62024 trial is an open label, randomised phase III trial.

Eligible participants are patients who had surgery to remove their gastrointestinal stromal tumours but were at moderate to high risk of relapse. Patients were randomised into two groups. One group would receive standard treatment, that is, observation and tests by their oncologist. The second group would receive adjuvant imatinib mesylate (400mg/day) for 2 years.

The main outcome measured was how long patients could continue before having to change to another treatment. This was compared between the two randomised groups. The investigators also measured the time to relapse and overall survival.

Patients were followed up for an average of nearly 5 years.

Contact Email

Principal Investigator

Associate Professor Dusan Kotasek (Adelaide Cancer Centre, SA)

More Information

Available online at the Australian New Zealand Clinical Trial Registry (ANZCTR) here.

Funding

European Organisation for Research and Treatment of Cancer (EORTC)