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Trastuzumab Has Altered Natural History of HER2-Positive Disease

Laino, Charlene

doi: 10.1097/01.COT.0000368897.37007.70

The introduction of trastuzumab has altered the natural history of HER2-positive disease, French researchers reported at the CTRC-AACR San Antonio Breast Cancer Symposium.

“Our findings show that even outside of a clinical trial, the addition of trastuzumab to chemotherapy improves the prognosis of metastatic breast cancer patients with HER2-positive disease,” said Veronique Dieras, MD, Chief of Clinical Research at Institut Curie.

“Prolongation of trastuzumab after progression with chemotherapy appears beneficial, even in patients with a high disease burden.”

The objective of the retrospective study was to explore the pattern of outcomes in a cohort of metastatic breast cancer patients treated with trastuzumab-based chemotherapy at the institute outside of a clinical trial setting.

Trastuzumab was approved in Europe in 2000 and by 2001, all HER2-positive patients at Institut Curie had access to the drug, she said.

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Study Population

The study involved all 245 women with metastatic breast cancer treated with trastuzumab there between 2001 and 2006. HER2-positivity was confirmed by immunohistochemistry or fluorescence in-situ hybridization.

The patients were classified into three groups: (1) those who received trastuzumab upfront, (2) those who received trastuzumab after one chemotherapy regimen, and (3) those who received trastuzumab after two or more chemotherapy regimens.

The median age of the patients was 53.9, and the median interval from primary tumor to first metastasis was 23 months. A total of 154 patients (63%) had visceral metastasis, and 122 (50%) presented with metastases at multiple sites; 101 patients (41%) developed brain metastasis during the course of their disease.

A total of 175 (72%) patients received trastuzumab as first-line therapy, and 70 (28%) were given the monoclonal antibody after a median of one line of chemotherapy. Over half—138 women, or 52%—of the patients received more than three chemotherapy regimens.

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Trastuzumab Extends Survival

The median overall survival time for all patients was 53 months and was similar in all three groups (53 months for patients who received trastuzumab upfront, 54 months for patients who received it after one line of chemotherapy, and 52 months for patients who received it after two lines of chemotherapy).

Patients who developed brain metastasis had a median survival time of 41 months, compared with 69 months for patients who did not have brain metastasis. The median survival time from first incidence of brain metastasis was 17 months.

Patients who developed visceral metastasis had a median survival time of 49 months, compared with 64 months for patients who did not have visceral metastasis.

“Still, 49 months is [a good outcome] in a population of women this ill,” Dr Dieras said. “Trastuzumab has altered the natural course of the disease even for women with the highest disease burden.”

Asked her opinion for this article, Minetta C. Liu, MD, Director of Translational Breast Cancer Research at Lombardi Comprehensive Cancer Center, commented that there is a lot of interest in combining trastuzumab with newer treatments to lower the rate of brain metastasis, since it does not cross the blood-brain barrier.

© 2010 Lippincott Williams & Wilkins, Inc.
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