In the first multi-center and international clinical trial conducted to better understand the complexities of a rare, aggressive and often lethal form of breast cancer, researchers have discovered that the experimental biological agent, lapatinib, successfully and specifically treats inflammatory breast cancer (IBC).

Massimo Cristofanilli, M.D., associate professor in the Department of Breast Medical Oncology at The University of Texas M. D. Anderson Cancer Center, reported the findings of the international Phase II trial today at the San Antonio Breast Cancer Symposium.

IBC is rare, representing just 1- 2 percent of all breast cancers diagnosed. Unlike other breast cancers that present as a lump, IBC’s symptoms include redness, swelling, and warmth in the breast, skin that is reddish, purple or bruised, has ridges and/or appears pitted like an orange. Other symptoms can include burning, aching or tenderness, an increase in breast size, and/or an inverted nipple.

A fast growing and aggressive cancer, IBC is more likely than other breast cancers to be misdiagnosed, often diagnosed after the disease has metastasized, says Cristofanilli. According to Cristofanilli, 40 percent of women with IBC will survive five years. Until now, no therapies specific to IBC have been studied in multi-center trials. As a consequence, no effective therapies - standard or experimental - exist for women with IBC.

“We initiated this Phase II study because lapatinib is one of the few drugs that had shown any activity in Phase I studies in patients with recurrent IBC. It appeared that this agent could be the first to offer hope for women newly diagnosed with the disease,” says Cristofanilli, the study’s principal investigator.

Lapatinib is an epidermal growth factor receptor and HER2neu tyrosine kinase inhibitor. An experimental drug that has shown promise in patients with metastatic HER2-positive cancer in whom Herceptin has failed, the oral agent blocks the activity of the HER2 protein as well as EGFR by binding to the part of the protein found inside breast cancer cells, explains Cristofanilli.

The trial enrolled 49 newly diagnosed IBC patients, all of whom were HER2 and/or EGFR-positive and who had never been treated for their disease. Approximately 25 percent of the women had metastatic disease.

The women received two weeks of daily lapatinib alone, followed by three months of concurrent lapatinib (taken daily) and paclitaxel chemotherapy (given weekly). Thirty-five of the patients completed the trial and had surgery, as indicated by the protocol, and constitutes the data presented.

The study reports that 30 out of the 35 patients, or 86 percent, had a clinical response, defined as 50 percent reduction in tumor size, to the lapatinib-chemotherapy drug regimen. Only one patient progressed during therapy. Three of the first 21 patients that had surgery had a complete pathological response, meaning that there was no evidence of disease at the time of surgery.

Just as interesting and important is the finding that 25-30 percent of the patients responded in the first two weeks when receiving lapatinib alone, says Cristofanilli.

“For IBC patients, these results should be very encouraging because there’s now more of a dedicated research effort for a type of breast cancer that has long been ignored and misunderstood. With lapatinib, we finally have a drug on which to build effective therapy - we just have to refine the most effective way to use it. The findings presented today will allow us to expedite future clinical trials.”

Planned studies with laptinib likely will include the agent in combination with different chemotherapy regimens. The trials also will focus on IBC patients who are HER2-positive, not EGFR positive, as indications from the Phase II trial showed that IBC patients who were HER2 positive responded better to the laptinib therapy.

Side effects to the laptinib were predictable and manageable, with diarrhea and a skin rash being the most common, he says.

In October, M. D. Anderson opened the first center in the world dedicated to IBC treatment and research. The clinic is under the co-direction of Cristofanilli and Thomas Buchholz, M.D., professor in the Department of Radiation Oncology, and is housed in M. D. Anderson’s Nellie B. Connally Breast Center.

Already, M. D. Anderson sees approximately 30 new cases of IBC a year - more than any other institution in this country, says Cristofanilli. With the new clinic, Cristofanilli and his team hope to see 60-80 new cases annually.

Lapatinib is manufactured by GlaxoSmithKline.

Source: University of Texas M. D. Anderson Cancer Center