The European Commission has approved an update to the  Novartis drug Glivec (imatinib) label to include 36 months of treatment after surgery for adults with KIT (CD117)-positive gastrointestinal stromal tumours (GIST) who met the inclusion criteria of the pivotal study. This extended treatment regimen has been shown to improve recurrence-free survival and overall survival for these patients with KIT+ GIST compared to patients who received 12 months of treatment after surgery.

Glivec (imatinib) is approved in more than 110 countries for the treatment of all phases of Ph+ CML, for the treatment of adult patients with KIT (CD117)-positive gastrointestinal stromal tumours (GIST), which cannot be surgically removed and/or have metastasized and for the treatment of adult patients following complete surgical removal of KIT+ GIST.

Adults with KIT+ GIST are at risk of recurrence following surgical removal of the primary tumour. Although complete surgical removal is possible in most patients with KIT+ GIST, many patients develop tumour recurrence or metastasis following surgery and survival following recurrence is poor. The newly updated label states that treatment with Glivec beyond 36 months may delay the onset of tumour recurrences further, while noting that an effect on overall survival has not been determined.

The EC decision follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) and applies in all 27 European Union (EU) member states, plus Norway and Iceland. Approval was based on data from an international, multi-centre, open-label, phase III clinical trial first presented at the 47th Annual Meeting of the American Society of Clinical Oncology (ASCO) plenary session in June 2011.

Results of the study showed that at five years, 66% of patients taking Glivec for three years after surgery for KIT+ GIST remained free of cancer recurrence compared to 48% who had received Glivec for only one year after surgery (p<0.0001). In addition, at five years, 92% of patients taking Glivec for three years after surgery were alive compared to 82% who had received Glivec for only one year after surgery (p=0.0187).

“This approval marks a key milestone in advancing the post-surgical treatment of GIST for certain patients in Europe, where Glivec is the only available therapy in this setting,” said Hervé Hoppenot, president, Novartis Oncology. “With this clinical evidence, physicians now have a strong basis for recommending three years of treatment for these patients with KIT+ GIST after surgery.”

Gastrointestinal stromal tumours, or GIST, are a rare, life-threatening cancer of the gastrointestinal tract. They are often difficult to diagnose and to treat because they may not cause any physical symptoms. In the EU, the incidence of GIST is estimated to be more than 5,000 cases each year.

This multi-centre, prospective, randomized study for the evaluation of adjuvant treatment with Glivec of histologically confirmed KIT+ GIST was conducted by the Scandinavian Sarcoma Group (SSG) and the Sarcoma Group of the Arbeitsgemeinschaft Internistische Onkologie (AIO).

The primary endpoint was to compare, within the first five years, recurrence-free survival in patients with a greater than 50% estimated risk of GIST disease recurrence, following diagnosis and treatment with adjuvant Glivec for either 12 or 36 months. The secondary endpoints included overall survival and treatment safety. Inclusion criteria for risk of recurrence was defined as tumour diameter >5.0 cm and mitotic count >5/50 high power fields (HPFs); or tumour diameter >10.0 cm, any mitotic count; or tumour of any size with a mitotic count >10/50 HPFs; or tumours ruptured into the peritoneal cavity.

Three hundred ninety-seven patients entered the study and the median follow-up was 54 months, from date of randomization to data cut-off. Recurrence-free survival was significantly longer in the 36-month group compared to the 12-month group (HR 0.46, 95% CI 0.32-0.65; p<0.0001; five-year recurrence-free survival 66% vs. 48%, respectively). Patients assigned to 36 months of Glivec had significantly longer overall survival (HR 0.45, 95% CI 0.22-0.89; p=0.0187; five-year overall survival 92% vs. 82%, respectively). Almost all patients experienced side effects while taking Glivec. Glivec was generally well tolerated. The proportion of patients who discontinued Glivec during the assigned treatment period for reasons other than GIST recurrence was 26% in the 36-month group and 13% in the 12-month group.

Novartis provided the study drug and supported the study financially. Additional funding was received from the Academy of Finland, Cancer Society of Finland, Sigrid Juselius Foundation and Helsinki University Research Funds.