Herceptin Plus Chemo Continues to Improve Survival

Early Results Show Herceptin Plus Chemotherapy after Surgery Reduces Risk of Recurrence in Women with Early-Stage, HER-2-Positive Breast Cancer

Special Release from Genentech, Inc., September 13, 2005

Is this for me? If you have HER2-positive early-stage breast cancer, you might want to read this article.

Background and importance of the study:Herceptin (chemical name: trastuzumab) works on breast cancers that make too much of the HER2/neu gene, or HER2, protein. These HER2-positive cancers tend to grow faster and are more likely to come back than HER2-negative breast cancers. About one out of every four breast cancers is HER2-positive.

Herceptin is approved by the U.S. Food and Drug Administration (FDA) for women with metastatic (advanced) HER2-positive breast cancer. The drug slows down or even stops the cancer's growth.

Herceptin can be given alone. And Herceptin may work even better when it is combined with chemotherapy.

In June 2005, breastcancer.org reported on two studies looking at Herceptin and chemotherapy to treat women with early-stage, lymph node-positive (cancer cells in the lymph nodes), HER2-positive breast cancer. The studies compared Herceptin plus chemotherapy to chemotherapy alone after surgery. After three years, compared to women who had only chemotherapy, women with early-stage, lymph node-positive, HER2-positive breast cancer who received chemotherapy plus Herceptin had a 52% lower rate of recurrence (the cancer coming back). This difference is statistically significant, meaning that the difference was likely due to Herceptin and not just to chance.

In the study reviewed here, researchers again compared Herceptin plus chemotherapy to chemotherapy alone in women with early-stage, HER2-positive breast cancer. But this study was different in two ways from the earlier ones:

• The earlier studies looked at one type of chemotherapy; in this study the researchers added Herceptin to two different chemotherapy regimens.
• The earlier studies at first enrolled only women with node-positive cancer. Women with node-negative cancer were enrolled later, and their results have yet not been reported. This study enrolled women with both node-positive and node-negative cancers from the start.

Study design: More than 3,000 women with early-stage, HER2-positive breast cancer were randomly assigned to receive one of three treatment plans after surgery:

1. Adriamycin (chemical name: doxorubicin) and Cytoxan (chemical name: cyclophosphamide) followed by Herceptin plus Taxotere (chemical name: docetaxel) (1,072 women).
2. Taxotere and Paraplatin (chemical name: carboplatin) plus Herceptin (1,056 women).
3. Adriamycin and Cytoxan followed by Taxotere (1,043 women).

Women with node-positive AND node-negative cancer were included in the study, but these early results do not tell us how many were in each group.

The researchers compared the groups for:

• disease-free survival (how long women live without return of the cancer), and
• cardiac side effects (both Adriamycin and Herceptin are known to have these side effects).

This study was funded by Sanofi-Aventis, which makes Taxotere, and Genentech, Inc., which makes Herceptin. The study was conducted by the Breast Cancer International Research Group.

Results: After about two years of follow-up, the researchers found that, compared to the women who received only chemotherapy (Adriamycin and Cytoxan followed by Taxotere):

• Women who received Adriamycin and Cytoxan followed by Herceptin plus Taxotere had a 51% lower risk of recurrence (the cancer coming back).
• Women who received Taxotere and Paraplatin followed by Herceptin had a 39% lower risk of recurrence.

These differences are statistically significant, meaning that the difference was likely due to Herceptin and not just to chance.

Because these are only early results, the researchers didn't have enough data to compare differences between the two groups who received Herceptin.

The researchers also found that 1.2% of the women who received Taxotere and Paraplatin plus Herceptin had congestive heart failure (weakening of the heart muscle that makes it unable to pump blood effectively). This percentage was the same for women who received chemotherapy alone. About 2.3% of the women who received Adriamycin and Cytoxan followed by Herceptin plus Taxotere had congestive heart failure.

Conclusions: The researchers concluded that giving chemotherapy PLUS Herceptin to women with early-stage, HER2-positive breast cancer improved disease-free survival (length of life without the cancer coming back). These therapies were given after surgery.

Take-home message: This is the fourth study to show that Herceptin plus chemotherapy lowers the risk of cancer coming back (recurrence) when compared to chemotherapy alone for women with early-stage, HER2-positive breast cancer after surgery.

This advance in breast cancer treatment is especially important because HER2-positive breast cancer tends to be more aggressive than HER2-negative disease. Still, it's important to keep in mind that these are early results. There are still many things we don't know about Herceptin, including:

• What are Herceptin's long-term effects? The four studies on Herceptin have followed women for at most four years (and some women for only two years). Researchers will continue to follow the women to answer this question.
• Does Herceptin work differently with different chemotherapy drugs? In this study, the researchers used Herceptin with two different chemotherapy regimens. Because these are early results, they didn't have enough data to compare the two treatments. But on the surface, it seems that Herceptin was more effective when it was given with Adriamycin and Cytoxan. This is important because Adriamycin is an anthracycline and is known to have cardiac side effects. Herceptin also is associated with cardiac side effects. Using Herceptin after Adriamycin may increase the risk for heart problems.
• Will Herceptin improve long-term survival and recurrence? More research is needed to find out whether the benefits seen in these early results will hold up over time.

If you have HER2-positive, early-stage breast cancer and have had surgery, you and your doctor now may be considering chemotherapy. You should seriously discuss the possible role of Herceptin. The discussion should include an in-depth look at any cardiac risk factors you may have.

Remember that every woman reacts differently to treatment. It's very important to find the right combination that you're comfortable with and that works best for YOU.

Stay tuned to breastcancer.org for the very latest information on Herceptin and other innovative treatments.