A significant minority of patients with advanced and aggressive cancer have survived more than 10 years after treatment with one of the first successful targeted cancer drugs.

Long–term results from a major international clinical trial reveal that a fifth of patients with advanced gastrointestinal stromal tumours (GIST) continue to survive a decade after first taking the targeted drug imatinib, also known as Glivec.

Some 10% of patients are still on the trial after 10 years, living free of any progression of their cancer – providing evidence that targeted cancer therapy can deliver dramatic, long–term responses even in patients with advanced cancer that has spread round the body.

Imatinib was the first example of a small–molecule targeted cancer treatment – a drug designed to hit specific cancer proteins – to be approved for use in patients, and the second successful targeted therapy overall, after the breast cancer drug Herceptin.

Since then many more targeted drugs have been developed but there has been debate over their true potential because of the tendency of cancers to evolve resistance against them.

Researchers at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, along with colleagues at 56 centres across Europe and Australia, conducted a phase III clinical trial of imatinib in 946 patients.

Their trial investigated the drug as a treatment for GIST, a rare tumour of the stomach or intestines, in patients where it had metastasised, or spread to other parts of the body.

The study was published in the Journal of Clinical Oncology, and was carried out by the European Organisation for Research and Treatment of Cancer (EORTC) and other international trials groups, with support from Novartis.

The study recruited patients in 2001–2 when treatment with imatinib was very new. It was set up to judge whether there was a survival benefit from taking 800mg of the drug daily, rather than the standard 400mg given to patients.

Researchers found that overall the increased dose had no extra overall survival benefit, although the disease was controlled for longer.

Patients in a small subgroup with a specific mutation in the gene KIT – one of the targets of the drug – were found to benefit from the increased dose. Their disease was under control for much longer, and the new follow–up data showed these patients lived longer as well.

Strikingly, a substantial minority of patients could continue to take either dose of the drug long term, without developing resistance to treatment.

Patients continued to take imatinib throughout because doctors did not want to take the risk that the disease might recur.

Study co–author Professor Winette van der Graaf, Professor of Personalised Oncology at the ICR, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said: “Since our study began, a wide range of targeted therapies have become available for many different types of cancer. Targeted cancer treatment has been a major step forward for patients, but unfortunately most drugs have only extended lives by months or a few years, because of the tendency of cancers to evolve resistance against them.

“It was remarkable to see 10% of the patients responding to imatinib for a decade without showing signs that the cancer was becoming resistant to treatment. Imatinib in GIST is still one of the best examples of active targeted agents and we should use these examples to better understand why this happens.”