New treatment?

[Clara]

New treatment developments point the way to improving survival in HER2/neu-positive breast cancer

MedWire - ASCO (Atlanta, GA, USA) June 3, 2006: Advances in the treatment of HER2/neu-positive disease are pointing the way to a new chapter in the management of this type of breast cancer, according to experts who presented their findings here at the American Society of Clinical Oncology meeting. This session was of such great importance that it was added to the program even after the deadline had passed for the submission of late-breaking research. The speakers focused on the findings of a phase III study showing that lapatinib may have a role in the treatment of advanced HER2/neu-positive disease that is resistant to trastuzumab, which is the only treatment thought to be effective in such cases.

“Yesterday in an education session I predicted that 5-10 years from now we’d have the tools we needed to eliminate mortality due to HER2/neu breast cancer,” said Dr. Eric Winer, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City who chaired the session. In the weeks preceding the conference, several investigators had concluded their research on targeted therapies for HER2/neu-positive disease.

Lapatinib blocks the activation of both the epidermal growth factor receptor (EGFR) and HER2 receptor by preventing phosphorylation. The rationale for the use of lapatinib in advanced breast cancer of this type is that the dual blockade of signalling may be more effective than the single-target inhibition seen with trastuzumab. The study, originally designed for a patient base of 518 patients, had a premature termination of enrolment because the interim analysis showed a clear advantage to patients treated with lapatinib, when combined with capecitabine.

In other research, investigators found that patients with early HER2/neu-positive disease benefited from treatment with trastuzumab after adjuvant chemotherapy. Trastuzumab has been shown to be effective in patients with advanced disease, and therefore, investigators wanted to know if it would be effective in treating early disease. Together, both findings showed the rewards of research focused on a particular disease, Dr. Winer said.

Lapatinib combined with capecitabine improves survival in advanced disease
Dr. Charles E. Geyer, Jr, Director of Breast Medical Oncology, Allegheny General Hospital, Pittsburgh, PA, USA

Women with advanced breast cancer who were treated with the targeted therapy agent lapatinib in combination with capecitabine had a time to progression that was twice as long as those treated with capecitabine monotherapy, Dr. Geyer said at the start of his presentation.

“These results show that lapatinib can help control the growth of breast cancers that are not being controlled by trastuzumab,” he said. The women in the study had breast cancers that had continued to progress despite treatment with trastuzumab.

“Trastuzumab is very effective for women with metastatic disease that produces large amounts of HER2/neu protein. However, because trastuzumab eventually stops controlling these cancers, there is a need for alternative treatments that block the function of HER2/neu in another way.”

In an open-label, phase III international, multicenter trial, Dr. Geyer and his co-investigators randomized patients with HER2/neu-positive metastatic breast cancer to be treated either with 1250 mg of continuous lapatinib daily and 2000 mg/m2 of capecitabine on days 1 to 14 every 3 weeks, or with capecitabine alone. Patients received treatment until their disease progressed or until they experienced unacceptable toxicity. The investigators followed the patients to determine disease-free and overall survival.

At the time of the interim analysis, the investigators were able to evaluate the records of 321 patients, among whom 93% had received other types of treatment. Those in the combination therapy group had a median time to progression of 36.9 weeks, compared to 19.7 weeks for the monotherapy group (p=0.00016). Within each group, 45 (28%) of the combination therapy group died, compared to 69 (43%) of the monotherapy group.

The most common adverse events were diarrhea, palmar-plantar erythrodysesthesia (PPE), and rash or other skin reactions. “Declines in left ventricular ejection fraction were infrequent, asymptomatic, and reversible,” said Dr. Geyer. “There were fewer patients with brain metastases as the first site of progression in the group receiving lapatinib.”

The results were so striking that the manufacturer of lapatinib is now seeking approval from the US Food and Drug Administration to use the drug on a compassionate-use basis in women with treatment-resistant HER2/neu-positive disease.

Is anybody taking this new drug?