Therapy with trastuzumab emtansine – a conjugate containing a recombinant HER2-receptor monoclonal antibody and a maytansinoid, which is now being used in numerous clinical trials involving patients with HER2-positive breast cancer—appears to cause nodular regenerative hyperplasia of the liver leading to portal hypertension in some patients, according to a report published online in the Journal of Clinical Oncology.
Two cases of this complication arising in women with recurrent or metastatic HER2-positive ductal carcinomas who were participating in phase II trials were reported by Dr. Jeremy Force and his associates at Indiana University, Indianapolis.
The first woman (age 66) received trastuzumab emtansine when breast cancer recurred despite initial lumpectomy with axillary lymph node dissection, chemotherapy, and radiation, then recurred again following multiple chemotherapy regimens. Abdominal CT showed a normal-appearing liver before trastuzumab emtansine was initiated. Months later the woman developed worsening abdominal pain and ascites, and noncirrhotic portal hypertension resulting from nodular regenerative hyperplasia was diagnosed. The therapy was discontinued, and the patient remains free of ascites 5 months later (J. Clin. Oncol. 2014 April 28 [doi:10.1200/JCO.2013.49.8543]).
The second woman (age 50) received trastuzumab emtansine when breast cancer metastasized 2 years after bilateral mastectomy and persisted despite multiple chemotherapy regimens. Abdominal CT showed only hepatic steatosis but no evidence of portal hypertension before trastuzumab emtansine was initiated. Within 1 month the patient showed elevated serum aminotransferase and thrombocytopenia but was asymptomatic. A surveillance CT 1 year later showed evidence of portal hypertension, and liver biopsy showed nodular regenerative hyperplasia. The therapy was discontinued, and within 1 month liver test results improved. The patient now shows no signs of ascites or liver decompensation, and thrombocytopenia has resolved.
Clinicians should maintain a high index of suspicion for drug-induced liver injury in patients undergoing treatment with trastuzumab emtansine and consider nodular regenerative hyperplasia if liver test abnormalities or signs of portal hypertension develop. "Early and accurate diagnosis is vital because both liver test abnormalities and portal hypertension seem to be reversible" when the drug is discontinued, Dr. Force and his associates said.
Dr. Force reported no financial conflicts of interest; his associates reported ties to Mochida, Genentech, Merck, Sanofi Aventis, Salix, Abbott, Eli Lilly, Pfizer, Vertex, Bristol-Myers Squibb, Intercept, and Gilead.