Tykerb Shows Benefit for HER2-positive, Herceptin-resistant Cancer

Reviewed study: "Tykerb Shows Benefit for HER2-positive, Herceptin-resistant Cancer" by Charles Guyer, Jr. and others, American Society of Clinical Oncology Annual Meeting, June 2006, Special Presentation.

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

What questions is the study trying to answer? The researchers wanted to know if women with advanced (metastatic) HER2-positive breast cancer that had stopped responding to Herceptin (chemical name: trastuzumab) would get benefits from taking a new medicine called Tykerb (chemical name: lapatinib) combined with Xeloda (chemical name: capecitabine).

Tykerb is a new experimental treatment that is not yet approved by the Food and Drug Administration (FDA).

Tykerb and Herceptin both are targeted therapies aimed at cancers that are HER2-positive, which means they make too much of the HER2/neu protein. While Herceptin blocks the protein on the cancer cell's surface, Tykerb blocks the protein inside the cell. Because it uses a different mechanism to work, researchers think Tykerb may be effective against HER2-positive cancers that have stopped responding to Herceptin.

Study design: The researchers studied 321 women with advanced HER2-positive breast cancer. The women all had been previously treated with:

• Herceptin,
• a taxane, such as Taxol (chemical name: paclitaxel) or Taxotere (chemical name: docetaxel), and
• an anthracycline, such as Adriamycin (chemical name: doxorubicin).

The cancer had stopped responding to these medicines, which means it had started growing again during or after taking these medications.

The researchers randomly split the women into 2 equal groups:

• 160 women took Tykerb and Xeloda,
• 161 women took Xeloda.

The women in both groups were similar:

• The average age was 52.
• About 90% of the women were white.
• About 85% had cancers that were hormone-receptor positive.
• More than 95% had stage IV cancer.

Both Tykerb and Xeloda are pills and taken orally. The women who took Tykerb took 1250 milligrams once daily continuously and Xeloda twice daily for 14 days every 3 weeks. The women who took only Xeloda took a slightly higher dosage, but in a similar fashion (twice daily for 14 days every 3 weeks). All the women received treatment until the cancer progressed or they experienced unacceptable side effects.

The women were evaluated every 6 weeks for the first 8 months, then every 12 weeks.

The researchers wanted to see if taking Tykerb combined with Xeloda would stop the cancer from growing for a longer time compared with just Xeloda. The researchers also wanted to see if Tykerb would lengthen overall survival (the time the women lived with or without the cancer progressing). They also wanted to know if Tykerb caused any side effects, especially heart problems, since Herceptin is known to cause heart problems.

The study began in March 2003 and was funded by GlaxoSmithKline, the manufacturer of Tykerb.

Study results: An interim analysis done in March 2006 showed that Tykerb combined with Xeloda doubled the time until the cancer grew, compared with Xeloda alone, in women with advanced, HER2-positive breast cancer that had stopped responding to Herceptin. The women who took Tykerb and Xeloda went about 8 and a half months before the cancer progressed. Women who took Xeloda alone went about 4 and a half months. This difference was statistically significant, which means it was probably because of the Tykerb and not just due to chance.

Because these early results were promising, the independent committee monitoring the study told the researchers to stop the study and offer Tykerb to all the women in the study.

These early results showed no difference in overall survival. Longer follow-up is needed to see if Tykerb helps women live longer.

The researchers found that Tykerb did not cause the serious heart problems that are associated with Herceptin. The women in the study had an echocardiogram every 6 weeks for the first 6 months of the study and then every 12 weeks for the rest of the study. Four women taking Tykerb and 1 woman taking only Xeloda had heart problems, but these problems were not severe. The women were treated and recovered.

The most commonly reported side effects from taking Tykerb with Xeloda were diarrhea, redness and tingling in the hands and feet, and a rash. These side effects were not severe and were treated successfully. Other side effects included stomach upset, vomiting, and fatigue. These were also low-grade.

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