The FINANCIAL -- Novartis
announced that following a priority review, the US Food and Drug
Administration has approved an update to the Glivec label to recommend 36 months of treatment after surgery for adult
patients with KIT positive gastrointestinal stromal tumors
who met the risk of recurrence inclusion criteria of the pivotal
trial, according to Novartis.
This treatment regimen has been shown to improve recurrence-free survival and overall survival for KIT+ GIST patients compared to 12 months of treatment.
The US approval was based on data from an international, multicenter, open-label, Phase III clinical trial. Results of the study showed that 36 months of Glivec treatment significantly prolonged RFS compared to 12 months of Glivec treatment, which was a 54% reduction in the risk of recurrence. In addition, 36 months of Glivec treatment resulted in a 55% reduction in the risk of death compared to one year of treatment. The median time of follow-up was 42 months for RFS and 48 months for OS.
Gastrointestinal stromal tumors are a rare, life-threatening cancer of the gastrointestinal tract. The major cause of GIST is an abnormal form of the protein KIT which causes cells to grow uncontrollably and become cancerous. Patients with GIST are at risk of recurrence following complete resection of primary GIST.
In August 2011, the US National Comprehensive Cancer Network updated its clinical practice guidelines to recommend consideration of at least three years of adjuvant therapy with Glivec for patients with high-risk GIST.
In addition to extending the Glivec label to three-year treatment duration in patients with KIT+ GIST after surgery, the FDA has agreed that all accelerated post-approval commitments for this indication have been met, confirming the clinical benefit of adjuvant treatment with Glivec. The SSG XVIII clinical trial was conducted by the Scandinavian Sarcoma Group and the Sarcoma Group of the Arbeitsgemeinschaft Internistische Onkologie. This trial was a multicenter, prospective, randomized study for the evaluation of adjuvant treatment with Glivec of histologically confirmed KIT+ GIST.
The primary endpoint of the study 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.
Three hundred ninety-seven patients entered the study. Inclusion criteria for risk of recurrence was defined as tumor diameter >5.0 cm and mitotic count >5/50 high power fields, or tumor diameter >10.0 cm, any mitotic count; or tumor of any size with a mitotic count >10/50 HPFs; or tumors ruptured into the peritoneal cavity.
Recurrence-free survival was longer in the 36-month group compared to the 12-month group. Patients assigned to 36 months of Glivec after surgery had longer overall survival . 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% over the full three- year treatment period 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.
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