HER2 Support Group Forums - anthracyclines on their way out of bc treatment?

due to cardiotoxicity and risk of leukemia outweighing benefit (particularly in those who are not topoIIa +):

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SABCS: Anthracycline May Be Superfluous in Breast Cancer Regimens

By Crystal Phend, Staff Writer, MedPage Today
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco
December 15, 2006

Additional SABCS Coverage

Dennis Slamon, M.D, Ph.D., UCLA

SAN ANTONIO, Dec. 15 -- Breast cancer patients may get similar benefit with less cardiotoxicity if the anthracycline Adriamycin (doxorubicin) is dropped from the adjuvant chemotherapy regimen containing Taxotere (docetaxel) and Herceptin (trastuzumab).

So found the second interim analysis of the Breast Cancer International Research Group study (BCIRG 006), reported Dennis Slamon, M.D., Ph.D., of the University of California in Los Angeles, at the San Antonio Breast Cancer Symposium.

The second interim analysis included 3,222 patients with early stage HER2-positive breast cancer followed for a mean of three years. The patients were randomized to receive adjuvant therapy consisting of Herceptin-Paraplatin-Taxotere or Adriamycin-Cytoxan-Taxotere-Herceptin or the control regimen Adriamycin-Cytoxan-Taxotere.

Disease-free survival advantage at three years was similar between the Herceptin-containing arms with and without Adriamycin (6% and 5%, respectively), he said.

There was a reduction in relative mortality for the Herceptin- and Adriamycin-containing arm (41%, P<0.0041 versus the regimen without Herceptin, designated as control) compared with the non-Adriamycin arm (34%, P<0.017 versus control).

However, the advantage was overshadowed by an increase in cardiac and leukemia toxicity in the Adriamycin- and Herceptin-containing arms compared with the arm without Adriamycin, Dr. Slamon said. There was five times the risk of significant cardiotoxicity in the Adriamycin- and Herceptin-containing arm compared with the non-Adriamycin arm.

Although Adriamycin has been a mainstay of breast cancer therapy, Dr. Slamon said, "If we are causing more problems than we are solving, I think we need to do something different." Some cardiologists have complained that with the use of anthracyclines, oncologists are merely exchanging death by breast cancer with death by congestive heart failure.

At baseline, patient characteristics were similar between arms with a mean age 49 and 54% hormone receptor positive and 29% axillary lymph node negative in each. By three years, there were 462 disease-free survival events including 185 deaths.

Compared to the control arm at the three year follow up, the researchers reported:

The relative reduction in the risk of relapse was 39% (P<0.001) for the Adriamycin- and Herceptin-containing arm and 33% (P=0.0003) for the Herceptin arm without Adriamycin,
The hazard ratios for disease free survival were 0.61 (95% confidence interval 0.48 to 0.76, P<0.0001) and 0.67 (95% CI 0.54 to 0.83, P=0.0003), respectively,
Overall survival was 92% for the Adriamycin- and Herceptin-containing arm and 91% for the non-Adriamycin Herceptin arm compared to 86% in the control arm, and
The hazard ratios for disease free survival were 0.59 (95% CI 0.42 to 0.85, P=0.004) and 0.66 (95% CI 0.47 to 0.93, P=0.017), respectively.

Regarding toxicity for the Adriamycin- and Herceptin-containing arm compared to the Herceptin arm without Adriamycin, the researchers reported:

Fewer cases of congestive heart failure (four versus 20, P=0.0015),
Fewer asymptomatic left ventricular ejection fraction declines (8.6 versus 18, P<0.0001),
Fewer cases of leukemia (four in Adriamycin-containing arms versus none in the non-Adriamycin arm),
More grade 3 and 4 thrombocytopenia (5.4% versus 1.2%), and
More grade 3 and 4 anemia (5.8% versus 3.1%).

"The 006 update for HER2 positive malignancies shows the difference in the number of disease free survival events and breast cancer deaths in favor of [Adriamycin-Cyclophosphamide-Taxotere-Herceptin], neither of which are statistically significant, is now exceeded by the number of critical adverse events," Dr. Slamon said.

He said this should raise the question as to what the role of anthracyclines are in the adjuvant treatment of breast cancer.

However, it may be premature to call for eliminating anthracyclines from the HER2 positive breast cancer armamentarium, said Shail Verma, M.D., of the Ottawa Cancer Center in Ottawa, who was uninvolved in the study.

"They are well on their way out," he said. "The last thing you want to see is a woman die in the adjuvant setting."

this report had the following addition:
Action Points
Explain to interested patients that the study suggests that Adriamycin may not be necessary in chemotherapy regimens containing Taxotere and Herceptin, but further study is needed.

This study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary as they have not yet been reviewed and published in a peer-reviewed publication.