Patients given adjuvant imatinib after surgery to remove gastrointestinal stromal tumours (GIST) experience increased recurrence-free survival (RFS) compared with those given placebo. These are the conclusions of authors of an Article published early Online and in an upcoming edition of The Lancet, written by Dr Ronald DeMatteo, Memorial Sloan-Kettering Cancer Center, New York, USA, and colleagues.
GIST is the most common soft tissue cancer of the intestinal tract, with around 3000-4000 cases per year in the USA. It typically occurs in the stomach or small intestine, but can occur occasionally in the rectum and rarely in the oesophagus or large intestine. Around 85% of these tumours test positive for a certain protein that allows them to be inhibited by imatinib.
This randomised, controlled phase III trial analysed patients who had a GIST at least 3cm in size which had tested positive for the protein, and who had had surgery to remove it. Patients were randomised to imatinib 400mg (359 pateints) or placebo (354 patients) once daily for a year after surgery. Patients given placebo were eligible to crossover to imatinib treatment if they experienced tumour recurrence.
The researchers found that at median follow-up of 19.7 months, 8% of patients in the imatinib group had had tumour recurrence or died, compared with 20% of in the placebo group. Imatinib significantly improved RFS compared with placebo (98% vs 83% at one year). The success of the treatment was dependent on the size of the tumour, with imatinib having the most impact on tumours of 10cm or larger, less of an effect on tumours between 6cm and 10cm, and the least effect on those between 3cm and 6cm. Imatinib was generally well tolerated, with the most common serious events being, in the imatinib group, dermatitis, abdominal pain, and diarrhoea; and, in the placebo group, hyperglycaemia.
The authors conclude: "In this phase III adjuvant trial of targeted therapy after the resection of localised, primary gastrointestinal stromal tumour, our findings have shown that imatinib increases recurrence-free survival. Our findings will affect the management of patients with primary gastrointestinal stromal tumour and could have relevance to the adjuvant use of other molecular agents for cancer."
In an accompanying Comment, Dr Peter Hohenberger, University of Heidelberg, Mannheim, Germany, says: "There are so many unknowns that this trial might not be able to provide a definitive treatment decision. To refine the indication for adjuvant treatment remains the big task for future studies."
For Dr Ronald DeMatteo, Memorial Sloan-Kettering Cancer Center, New York, USA please contact Jeanne D'Agostino T) +1 212 639-3573 E) dagostij@mskcc.org / dematter@mskcc.org
Dr Peter Hohenberger, University of Heidelberg, Mannheim, Germany T) +49 177 5454882 E) peter.hohenberger@chir.ma.uni-heidelberg.de
For full Article and Comment, see: http://press.thelancet.com/stromaltumour.pdf
Journal
The Lancet