Iressa (gefitinib) - Advisories, Warnings, and Recalls for Health Professionals

Help on accessing alternative formats, such as Portable Document Format (PDF), Microsoft Word and PowerPoint (PPT) files, can be obtained in the alternate format help section.

Contact BMORS

Health Canada Endorsed Important Safety Information on Iressa (gefitinib)

December 1, 2006

Dear Health Care Professional:

Subject: Lack of Survival Benefit and Increased Incidence of Tumour Haemorrhage in Association with IRESSA^® in Patients with Squamous Cell Carcinoma of the Head and Neck (SCCHN)

AstraZeneca, following discussions with Health Canada, would like to inform you of new safety information regarding IRESSA. IRESSA is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Although IRESSA is indicated for the treatment of locally advanced non-small cell lung cancer in patients who have failed two prior chemotherapy regimens, its use has been restricted by Health Canada to patients who are currently benefiting from IRESSA and whose tumours are EGFR expression status positive or unknown. For continued supply of the drug, patients have had to be registered by a pharmacist into the IRESSA Patient Registry (IPR) program. Head and neck cancer is not an approved indication for IRESSA, but patients with this diagnosis could have been registered if benefiting from therapy.

This letter is to inform you, a Health Care Professional involved in the IPR, of the top-line results from an IRESSA study in patients with squamous cell carcinoma of the head and neck (SCCHN) entitled: A Phase III randomized, stratified, parallel-group, multi-centre, comparative study of IRESSA 250 mg and 500 mg versus methotrexate for previously treated patients with squamous cell carcinoma of the head and neck (1839IL/0704, IMEX).

The objectives of the IMEX trial were to examine the efficacy and safety/tolerability of IRESSA 250 mg and 500 mg versus methotrexate in a refractory, unselected population of patients with recurrent SCCHN. A total of 486 patients were recruited from approximately 100 centres worldwide; 483 patients were evaluable for safety. The trial was designed to demonstrate superiority for IRESSA versus methotrexate for the primary endpoint of overall survival (OS). The trial results did not demonstrate an improvement in survival for IRESSA 250 mg or 500 mg compared to methotrexate, although there was some evidence of anti-tumour activity as measured by response rate. There was a numerical advantage for patients randomized to methotrexate, which did not reach statistical significance. The median survival times were consistent with published data for active monotherapy treatments in the recurrent disease setting and are presented below:

• IRESSA 250 mg versus methotrexate OS: Median OS 5.6 vs. 6.7 months (HR 1.22; 95% CI 0.95 to 1.57; p= 0.1205)
• IRESSA 500 mg versus methotrexate OS: Median OS 6.0 vs. 6.7 months (HR 1.12; 95% CI 0.87 to 1.43; p= 0.3899)

Analysis of the safety data from the IMEX trial identified a potential new safety finding of "tumour haemorrhage" in patients treated with IRESSA 250 mg and 500 mg. The incidence of tumour haemorrhage seen in the IRESSA 250 mg & 500 mg treated patients was; 8.9% (n=14/158) and 11.4% (n=19/166) respectively, compared to 1.9% (n=3/159) seen in the methotrexate treated patients. The majority of these tumour haemorrhages were considered by the reporting physician to be mild to moderate in nature (CTC grades 1 or 2), and resolved whilst study treatment continued. Of the 36 patients with tumour haemorrhage, 3 died as a result of their tumour haemorrhage; 2 of these 3 patients were receiving IRESSA 250 mg and the third was receiving IRESSA 500 mg. These 3 cases were not considered by the reporting physician to be causally related to IRESSA therapy.

AstraZeneca is undertaking a comprehensive review of the IMEX study data to fully understand the significance of these findings. As a Health Care Professional involved in the IRESSA Patient Registry program, Health Canada, in collaboration with AstraZeneca, has requested that you be made aware of the IMEX trial results and that you communicate these results to any patient currently receiving IRESSA for the treatment of SCCHN.

Managing marketed health product-related adverse reactions depends on health care professionals and consumers reporting them. Reporting rates determined on the basis of spontaneously reported post-marketing adverse reactions are generally presumed to underestimate the risks associated with health product treatments. Any occurrence of serious and/or unexpected adverse reactions in patients receiving IRESSA should be reported to AstraZeneca Canada Inc., or Health Canada, at the following addresses:

Should you have any questions or require additional information regarding IRESSA^®, please contact AstraZeneca Medical Information at 1-800-668-6000 (English) and/or 1-800-461-3787 (French).

AstraZeneca Canada Inc.

Original Signed by:

Kazi Borkowski,
Vice-President Medical Affairs

IRESSA^® and the AstraZeneca logo are trademarks of the AstraZeneca group of companies.