Health Canada Approves A New Treatment Option For Patients With Gastrointestinal Stromal Tumours (GIST), A Rare Form Of Sarcoma

Stivarga^® (regorafenib tablets) receives expanded approval to include Gastrointestinal Stromal Tumours (GIST) after being approved for metastatic colorectal cancer earlier this year

TORONTO, Oct. 17, 2013 /CNW/ - Bayer Inc. announced today Health Canada's expanded approval of Stivarga^® (regorafenib tablets) to now include treatment of adult patients with metastatic and/or unresectable gastrointestinal stromal tumors (GIST) who have had disease progression on or intolerance to imatinib mesylate and sunitinib malate treatment.¹ Stivarga was approved in March 2013 for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-based chemotherapy, oxaliplatin, irinotecan, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy.²

A Gastrointestinal Stromal Tumour (GIST) is a soft-tissue sarcoma of the gastrointestinal tract. Soft-tissue sarcomas are solid tumours that develop from connective tissue cells. GIST is the most common sarcoma of the GI tract and most commonly arises in the stomach or small intestine. It is estimated that 500 Canadians are diagnosed with GIST each year³ and they most often occur in people over age 50, although they may develop at any age. The exact cause of GISTs is not known.⁴ Early-stage disease can be surgically resected, but more than 40 per cent of cases recur and metastasize.⁵

Currently available treatments may provide patients with success in the management of their disease for a period of time, but research highlights about 80 per cent of patients eventually experience disease progression.⁶

"Stivarga represents a significant development for patients with metastatic GIST. It is important that patients who are no longer responding to treatment have another tool to manage this disease," says Dr. Martin Blackstein, MD PhD, Associate Professor of Medicine at the University of Toronto and Staff Medical Oncologist at Mt. Sinai Hospital. "The approval of Stivarga to treat GIST is yet another example of continued research and development.  New compounds such as Stivarga that have been studied in clinical trials provide an effective option for patients, especially when there was nothing else left to offer them."

The Health Canada approval of Stivarga in GIST is based on data from the pivotal Phase III GRID (GIST - Regorafenib In Progressive Disease) trial, which showed that Stivarga plus best supportive care (BSC) had a statistically significant advantage in progression-free survival (PFS) compared to placebo plus BSC (HR=0.27 [95% CI 0.19,0.39: p<0.0001]. The median PFS was 4.8 months in the Stivarga arm versus 0.9 months in the placebo arm.

"One of the hardest conversations with patients and caregivers comes when someone is doing their very best to battle this devastating disease and they've run out of treatment options," says Diana Arajs, Chair of the Sarcoma Cancer Foundation of Canada. "Every advancement when it comes to the availability of new treatments represents hope to the patient and their family and is a significant advancement for our community."

"Bayer is an organization dedicated to providing patients with cutting-edge science to treat a variety of different diseases," says Christian Lauterbach, President & CEO of Bayer Inc. in Canada. "The approval of Stivarga to treat GISTs represents another option for patients and builds on Bayer's commitment and offering in the oncology arena with treatments already available in Canada for kidney, liver and colon cancer."

About Gastrointestinal Stromal Tumour (GIST)
GIST is the most common form of sarcoma (a type of cancer that develops from certain tissues, like bone or muscle) involving the gastrointestinal tract. In Canada, it is estimated that there are approximately 500 new cases of GIST diagnosed each year.⁷ Especially in the early stages, GIST may not cause any symptoms and may be found incidentally when the doctor is looking for other problems.³

About the GRID Study⁸
GRID was a multicentre randomized, double-blind, placebo-controlled, Phase III study of regorafenib for the treatment of treatment refractory GIST. It randomized 199 patients with metastatic and/or unresectable GIST. Patients were randomized in a 2:1 ratio to receive regorafenib plus BSC or placebo plus BSC to evaluate efficacy and safety. Treatment cycles consisted of 160 mg regorafenib once daily orally for three weeks on / one week off plus BSC (N=133) or matching placebo plus BSC (N=66) in the double blind period of the study. Patients continued therapy until disease progression or unacceptable toxicity. After progression all patients were given the option to go onto regorafenib until subsequent progression. The primary endpoint was PFS, and a key secondary outcome measure was overall survival (OS). At the time of the database lock for publication, the HR (Hazard Ratio) for OS was in favour of patients randomized to the Stivarga arm (0.77, 95% CI 0.42-1.41;p=0.199); however, there was no significant difference in overall survival between the Stivarga plus BSC group and the placebo plus BSC group, and the median OS had not yet been reached.

About Stivarga^® (Regorafenib tablets)⁹
Stivarga is indicated for the treatment of patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumour (GIST) who have been previously treated with imatinib mesylate and sunitinib malate. It is also indicated for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy.¹

Stivarga is an inhibitor of multiple kinases involved in normal cellular functions and in pathologic processes such as oncogenesis, tumour angiogenesis, and maintenance of the tumour microenvironment.

Safety and adverse events were similar to those observed with other tyrosine kinase inhibitors (TKIs).¹ The most frequently observed adverse drug reactions (≥ 30%) in Stivarga-treated patients vs. placebo-treated patients in GIST, respectively, were: hand-foot skin reaction (HFSR) / palmar-plantar erythrodysesthesia (PPE) syndrome, hypertension, asthenia/fatigue, diarrhea, dysphonia, infection, decreased appetite and food intake, and rash. The most serious adverse drug reactions in patients receiving regorafenib are severe liver injury, hemorrhage, cardiac ischemia/infarction, hypertension, reversible posterior leukoencephalopathy syndrome (RPLS), Stevens-Johnson syndrome/toxic epidermal necrolysis, and gastrointestinal perforation or fistula.¹¹

About Bayer Inc.
Bayer Inc. is a Canadian subsidiary of Bayer AG and the headquarters for the Canadian operations.  Celebrating its 150 anniversary, Bayer AG is an international research-based group with core businesses in healthcare, crop science and innovative materials committed to creating a better life for all through science.

In Canada, Bayer operates its healthcare business - Pharmaceuticals, Consumer Care, Diabetes Care, Animal Health and Radiology & Interventional - from its headquarters in Toronto, ON and its CropScience business from Calgary, AB.

With more than 1,300 employees across the country, in 2012, Bayer had sales of $1.6 billion CDN and invested $55.9 million CDN in research and development in Canada. Globally, Bayer AG had sales of $39.8 billion Euro and invested $3 billion Euro in research and development. For more information about Bayer Inc., please visit www.bayer.ca.

Forward-Looking Statements
This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer Group or subgroup management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer's public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

REFERENCES
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¹ Canadian Stivarga Product Monograph, October 2013
² Canadian Stivarga Product Monograph, October 2013
³ http://www.liferaftgroup.ca/home/what-is-gist/
⁴ http://www.cancer.ca/en/cancer-information/cancer-type/soft-tissue-sarcoma/pathology-and-staging/types-of-tumours/malignant-tumours/gastrointestinal-stromal-tumour-gist/?region=on
⁵ Effi cacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial
⁶ Effi cacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial
⁷ http://www.liferaftgroup.ca/home/what-is-gist/
⁸ Effi cacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial
⁹ Canadian Stivarga Product Monograph, October 2010
¹⁰ Grothey, et al. The Lancet 21 Nov 2012 doi: 10.1016/S0140-6736(12)61900-X Page 8
¹¹ Canadian Stivarga Product Monograph, October 2013

SOURCE: Bayer Inc.

For further information:

Emily Hanft, Bayer
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416-240-5466

Ethan Pigott, beSPEAK Communications
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416-558-2783