Herceptin clinical trials: past, present and future

Herceptin is the humanized monoclonal antibody targeting the Her-2-Neu oncogene, which, when amplified, connotes a poor prognosis for the 25% of breast cancer patients with gene amplification. Pivotal clinical trials in metastatic breast cancer have established clinical benefit in approximately one-third of patients treated with one or two prior chemotherapy regimens for metastatic disease; almost half of patients when used as a first-line single agent; and in even higher percentages when used in combination with cytotoxic chemotherapy. Antitumor response rates can be maximized by selecting patients for treatment based on gene amplification tests (eg FISH) rather than on immunohistochemistry. Although Herceptin is very well tolerated subjectively, it was, unexpectedly, found to be cardiotoxic, especially when used in conjunction with anthracyclines. This finding has made the development of adjuvant programs a challenge, but several such adjuvant protocols in earlier stage disease are in progress or planned. In addition to adjuvant protocols, newer Herceptin combinations with other cytotoxics and hormonal therapy will also be discussed. Herceptin is the first (hopefully of many) targeted therapies that could revolutionize breast cancer therapy in the decade to come.