- First large Phase III study to demonstrate significant survival benefits of extending treatment with Glivec for three years compared to one year following surgery
- Important finding for treatment of KIT+ GIST patients who are at risk of recurrence following complete resection of primary tumor
- Publication follows European Commission approval of new label based on these data
Basel, March 27, 2012 - The Journal of the American Medical Association (JAMA) today published a Phase III study that showed significant survival benefits for patients meeting the study inclusion criteria who received three years of treatment with Glivec® (imatinib) after surgery to remove KIT (CD117)-positive gastrointestinal stromal tumors (KIT+ GIST) compared to one year of treatment. The study results were first presented at the 47th Annual Meeting of the American Society of Clinical Oncology (ASCO) plenary session in June 2011.
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.
According to data published in JAMA from this international, multicenter, open-label Phase III clinical trial, at five years, 66% of patients taking Glivec for three years after surgery for KIT+ GIST remained free of recurrence (RFS) compared to 48% who had received Glivec for only one year after surgery (p<0.001; HR 0.46, 95% CI 0.32-0.65). In addition, at five years, 92% of patients taking Glivec for three years after surgery were alive (OS) compared to 82% who had received Glivec for only one year after surgery (p=0.02; HR 0.45, 95% CI 0.22-0.89). Four hundred patients entered the study. Median patient follow-up was 54 months.
Based on this data, in February 2012, the European Commission approved an update to the Glivec label to include three years of treatment after surgery for adults with KIT+ GIST.
"This study shows a significant recurrence-free survival benefit in adults with KIT+ GIST from adjuvant treatment with Glivec and provides important evidence to inform the clinical care of these patients after surgery," said Heikki Joensuu, M.D., Ph.D., Professor, Oncology, University of Helsinki. "These data are likely to result in a new standard of care for these patients."
About the SSG Phase III trial
This multicenter, 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 tumor diameter >5.0 cm and mitotic count >5/50 high power fields (HPFs); or tumor diameter >10.0 cm; or tumor of any size with a mitotic count >10/50 HPFs; or tumors ruptured into the peritoneal cavity.
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 25.8% 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.
About Glivec (imatinib)
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 tumors (GIST), which cannot be surgically removed and/or have metastasized and for the treatment of adult patients following complete surgical removal of KIT+ GIST.
Glivec Important Safety Information
Glivec can cause fetal harm in pregnant woman. Glivec has been associated with severe edema (swelling) and serious fluid retention. Cytopenias (anemia, neutropenia, thrombocytopenia) are common, generally reversible and usually managed by withholding Glivec or dose reduction. Monitor blood counts regularly. Severe congestive heart failure and left ventricle dysfunction, severe liver problems including cases of fatal liver failure and severe liver injury requiring liver transplants have been reported. Use caution in patients with cardiac dysfunction and hepatic dysfunction. Monitor carefully.
Bleeding may occur. Severe gastrointestinal (GI) bleeding has been reported in patients with KIT+ GIST. Skin reactions, hypothyroidism in patients taking levothyroxine replacement, GI perforation, in some cases fatal and tumor lysis syndrome, which can be life threatening, have also been reported with Glivec. Correct dehydration and high uric acid levels prior to treatment. Long-term use may result in potential liver, kidney, and/or heart toxicities; immune system suppression may also result from long-term use. In patients with hypereosinophilic syndrome and heart involvement, cases of heart disease have been associated with the initiation of Glivec therapy. Growth retardation has been reported in children taking Glivec. The long-term effects of extended treatment with Glivec on growth in children are unknown.
The most common side effects include fluid retention, muscle cramps or pain and bone pain, abdominal pain, loss of appetite, vomiting, diarrhea, decreased hemoglobin, abnormal bleeding, nausea, fatigue and rash. Glivec should be taken with food and a large glass of water.
Please see full Prescribing Information.
The foregoing release contains forward-looking statements that can be identified by terminology such as "positive opinion," "likely," or similar expressions, or by express or implied discussions regarding potential new indications or labeling for Glivec or regarding potential future revenues from Glivec. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with Glivec to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Glivec will be approved for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that Glivec will achieve any particular levels of revenue in the future. In particular, management's expectations regarding Glivec could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures; unexpected manufacturing issues; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
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|||Joensuu H, et al. One Versus Three Years of Adjuvant Imatinib for Operable Gastrointestinal Stromal Tumor. JAMA. Vol 307, No.12. March 28, 2012.|
|||Joensuu H, et al. Twelve vs. 36 months of adjuvant imatinib (IM) as treatment of operable GIST with a high risk of recurrence: Final results of a randomized trial (SSGXVIII/AIO). 47th Annual Meeting of the American Society of Clinical Oncology. Abstract No. LBA1. June 5, 2011.|
|||American Cancer Society. Cancer Reference Information. Detailed Guide for Gastrointestinal Stromal Tumors. http://www.cancer.org/acs/groups/cid/documents/webcontent/003103-pdf.pdf. Accessed on January 23, 2012|
|||National Comprehensive Cancer Network (NCCN): Clinical Practice Guidelines in Oncology: Soft Tissue. Version 2, 2011.|
|||Study Comparing 12 Months Versus 36 Months of Imatinib in the Treatment of Gastrointestinal Stromal Tumor (GIST). Available at: http://clinicaltrials.gov/show/NCT00116935. Accessed on January 9, 2012.|
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 Known as Gleevec® (imatinib mesylate) tablets in the US, Canada and Israel.