Health Canada approves first post-surgical treatment for patients with gastrointestinal stromal tumours

Patients with gastrointestinal stromal tumours (GIST) can now take action at an earlier stage of this rare form of cancer to reduce the risk of their disease returning following surgery. Novartis Pharmaceuticals Canada announced today that Gleevec* (imatinib mesylate) has received conditional approval by Health Canada for the adjuvant (post-surgical) treatment of adult patients who are at intermediate to high risk of disease recurrence following the surgical removal of GIST.

Gleevec* is now the only adjuvant treatment indicated to delay or prevent the return of this highly aggressive cancer, filling a major unmet medical need and giving new hope to GIST patients. Clinical study results published in The Lancet in March, 2009 showed the risk of GIST recurring is reduced by 89% as a result of using adjuvant therapy with Gleevec*, with an almost two-fold longer recurrence-free survival (RFS) compared to placebo.(1)

GIST is a life-threatening disease, and the most common form of gastrointestinal tract cancer. After initial removal, GIST tumours can return in as many as one of two patients.(2) Recurrent GISTs are often more aggressive than primary tumours, with relapses associated with lower survival rates.(3)

"Prior to this approval, observation has been the standard of care after surgical removal of primary GIST, with a significant number of patients facing postoperative recurrence or metastasis of their disease," said Dr. Martin Blackstein, Medical Oncologist, Mount Sinai Hospital in Toronto. "The approval of Gleevec in the adjuvant setting impacts the course of the disease by delaying, and in some cases preventing, disease recurrence."

Gleevec* is now approved for 10 indications, including the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) and Kit (CD117)-positive gastrointestinal stromal tumours which cannot be surgically removed and/or have already spread to other parts of the body (metastasized).(4)

Filing data

This approval was based on data from a National Cancer Institute-sponsored Phase III study that showed a dramatic reduction after one year in the return of GIST after surgery in patients treated with Gleevec* versus placebo. The final data from the study, as published in The Lancet, showed an estimated one-year, recurrence-free survival of 98% for GIST patients taking Gleevec versus 83% taking placebo.(1)

The study was a double-blind, randomized, multicentre, international study of more than 700 GIST patients throughout the US and Canada who had undergone surgery to remove their tumours. The primary efficacy endpoint of the study was recurrence-free survival (RFS), defined as the time from the date of randomization to the date of recurrence or death from any cause. Participants were randomized to receive either Gleevec* 400 mg/day or a matching placebo for one year.(1)

With a median follow-up of 19.7 months, there were 30 RFS events out of 359 patients in the Gleevec* arm (8%) compared to 70 RFS events out of 354 patients in the placebo arm (20%) (hazard>

The study, known as ACOSOG Z9001, was conducted at multiple cancer centres, including centres in Canada, under a Cooperative Research and Development Agreement between Novartis and the National Cancer Institute. The study was led by the American College of Surgeons Oncology Group (ACOSOG) in association with the Duke Clinical Research Institute.(1)

The investigators reported that Gleevec* therapy was generally well tolerated by most patients, with side effects similar to those observed in previous clinical trials with Gleevec*. The most frequently reported adverse reactions were diarrhea, fatigue, nausea, edema, decreased hemoglobin, rash, vomiting and abdominal pain. No new adverse reactions were reported in the adjuvant GIST treatment setting that had not been previously reported in other patient populations including patients with unresectable and/or malignant metastatic GIST.(1)