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Trastuzumab Adds to Docetaxel Activity in Metastatic Breast Cancer: Presented at SABCS

By Robert H. Carlson

SAN ANTONIO, TX -- December 8, 2003 -- Adding the monoclonal antibody trastuzumab (Herceptin) to docetaxel monotherapy for breast-cancer patients at first recurrence virtually doubles the median survival, according to results from a multinational randomized trial described here at the 26^th Annual San Antonio Breast Cancer Symposium.

"This is [a] very important [finding] to know in patients who have over-expression of the human epidermal growth factor receptor 2 (HER2) gene," said investigator Stephen Chan, MD, consultant oncologist, Nottingham City Hospital, United Kingdom.

Trastuzumab targets the HER2 gene, which is over-expressed in 20% to 25% of metastatic breast-cancer patients. Dr. Chan noted that HER2-positive breast cancer is a very aggressive disease. Subjects had HER2-positive metastatic breast cancer not already treated for recurrence, and had at least 1 measurable lesion.

Dr. Chan reported that the median survival for 94 patients taking docetaxel alone was 18.3 months in the trial, compared with 27.7 months for the 92 women taking the combination. "That's the bottom line," he stated.

The P value of the comparison data was.0002, indicating very significant data with little chance that the findings were coincidental.

Importantly, trastuzumab added very little to the side-effect profile of the treatment. "Conceptually, [the combination] is attractive in practice because you are getting a benefit without a huge loss to side effects," Dr. Chan noted.

HER2 testing was conducted locally or in a reference laboratory with fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC). If the latter was used, patients had to have been IHC 3 positive, although IHC 2 positivity was allowed at the beginning of the study.

Patients were randomized to either intravenous docetaxel alone at 100mg/m² every 3 weeks for 6 cycles, or to docetaxel plus trastuzumab. Trastuzumab was given intravenously at a loading dose of 4 mg/kg followed by a 2 mg/kg weekly dose until disease progression.

If patients in the docetaxel-alone study arm progressed, they could then be given trastuzumab. Tumor response was assessed according to World Health Organization (WHO) criteria by the investigator and an independent radiological review board.

The trastuzumab-docetaxel regimen caused no unexpected toxicities, Dr. Chan said, and the rate of congestive heart failure (CHF) was only 1%. This compares favorably with rates for trastuzumab plus paclitaxel, a standard regimen for this stage disease, Dr. Chan said.

The incidence of febrile neutropenia or neutropenic sepsis was approximately the same for both study arms.

Dr. Chan said only minor asymptomatic decreases in left ventricular ejection fraction (LVEF) were common in both study arms, but Dr. Chan said these were of uncertain significance.

One patient on combination therapy did develop CHF about 5 months after starting on treatment, but before study entry the patient had received a prior cumulative dose of adjuvant doxorubicin of 300mg/m², a drug known for cardiotoxicity at higher cumulative doses.

The trial, conducted in the United Kingdom, France, Italy, Switzerland and Australia, was sponsored by Hoffman-La Roche.


[Study Title: First-line trastuzumab (Herceptin® plus docetaxel versus docetaxel alone in women with HER2-positive metastatic breast cancer (MBC): results from a randomised phase II trial (M77001). Abstract 217]

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