Herceptin Should Be Used With Caution In Pulmonary Compromised Patients

Genentech is revising Herceptin labeling to add warnings about fatal hypersensitivity, infusion and pulmonary reactions in breast cancer patients being treated with the anti-HER2 oncologic.

On May 3, the company alerted physicians that 62 postmarketing reports of serious adverse events with Herceptin (trastuzumab) have been received, including 15 deaths. About 25,000 people have been treated with Herceptin.

"Most patients with fatal events had significant pre-existing pulmonary compromise secondary to intrinsic lung disease and/or malignant pulmonary involvement....These patients should be treated with extreme caution," Genentech's "Dear Doctor" letter states.

"Fifteen patients experienced pulmonary and other adverse events following Herceptin use, which culminated in a fatal outcome," the letter states. Nine of these patients developed adverse reactions within 24 hours of infusion.

Most of the adverse events occurred during infusion with Herceptin or up to 12 hours following infusion. Some of the adverse events occurred more than 24 hours after infusion.

"In some cases, patients improved after the initial reaction, but experienced marked clinical deterioration at a later time point," the warning letter states. "In a small number of cases, the patients died at home."

The postmarketing reports include events not previously seen in clinical trials: adult respiratory distress syndrome, anaphylaxis and death within 24 hours of infusion.

Previously reported events that occurred with greater severity postmarketing include: urticaria, bronchospasm, angioedema, hypotension, dyspnea, wheezing, pleural effusions, pulmonary infiltrates, noncardiogenic pulmonary edema and pulmonary insufficiency and hypoxia, the company said.

Genentech is working with FDA to update the product labeling. Additions will be made to the boxed warning, warnings and adverse reactions sections.

This is the second "Dear Doctor" letter the company issued for Herceptin. A letter was sent to healthcare providers Sept. 23, 1999 to clarify instructions for reconstituting Herceptin (¹ (Also see "Genentech Herceptin" - Pink Sheet, 18 Oct, 1999.)).