Experimental Medicine Plus Carboplatin Helps Treat Triple-Negative Disease

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A study has found that the experimental targeted therapy veliparib plus the chemotherapy carboplatin followed by traditional chemotherapy medicines before surgery for triple-negative breast cancer offers more benefits than traditional chemotherapy medicines alone before surgery.

The study, “Veliparib/carboplatin plus standard neoadjuvant therapy for high-risk breast cancer: First efficacy results from the I-SPY 2 TRIAL,” was presented by Hope Rugo, clinical professor of medicine and director of the Breast Oncology Clinical Trials Program at the University of California-San Francisco Helen Diller Family Comprehensive Cancer Center, on Dec. 13, 2013 at the 2013 San Antonio Breast Cancer Symposium. Dr. Rugo is a member of the Breastcancer.org Professional Advisory Board.

Veliparib is a type of targeted therapy medicine called a PARP inhibitor. DNA carries genetic information in both healthy cells and cancer cells. Cells can develop DNA damage spontaneously or from exposure to specific things in the environment (too much sun, for example) that make DNA damage more likely to happen. But cells can detect and repair damage to DNA. When DNA is damaged in a healthy cell and the damage isn't fixed, that cell can become cancerous. The poly ADP-ribose polymerase (PARP) enzyme fixes DNA damage in both healthy and cancer cells. Researchers believe that a medicine like veliparib, which interferes with (inhibits) the PARP enzyme, might make it even harder for cancer cells to fix DNA damage. This would make it harder for the cancer cells to survive.

Carboplatin is the only platinum-based chemotherapy medicine approved by the U.S. Food and Drug Administration (FDA) to treat breast cancer. Platinum-based chemotherapy weakens or destroys breast cancer cells by damaging the genetic material in the cells and making it hard for cells to repair any genetic damage. Carboplatin is used to treat advanced-stage breast cancer and is usually given in combination with other chemotherapy medicines.

In this study, called I-SPY 2, researchers looked at 115 women diagnosed with early-stage breast cancer that was 2.5 cm or larger and was considered at high risk for coming back (recurrence) based on a MammaPrint genomic test score, or were diagnosed with triple-negative or HER2-positive breast cancer regardless of MammaPrint results.

Triple-negative breast cancer is:

  • estrogen-receptor-negative
  • progesterone-receptor-negative
  • HER2-negative

About 15% to 20% of breast cancers are triple-negative. Triple-negative cancers usually are more aggressive, harder to treat, and more likely to come back than cancers that are hormone-receptor-positive and/or HER2-positive. Hormonal therapy and the targeted therapies Herceptin (chemical name: trastuzumab), Tykerb (chemical name: lapatinib), and Perjeta (chemical name: pertuzumab) usually don't work on triple-negative breast cancer.

Because triple-negative breast cancer is aggressive and there are a limited number of treatment choices, doctors are looking for new ways to treat it, especially early-stage triple-negative disease.

HER2-positive breast cancers have too many copies of the HER2/neu gene, which make too much of the HER2 protein. HER2-positive breast cancers tend to be more aggressive than cancers that are HER2-negative. Herceptin, Tykerb, and Perjeta are used to treat HER2-positive breast cancer.

The researchers also kept track of each cancer’s hormone receptor status.

The women in the study were randomly assigned to get either:

  • veliparib plus carboplatin in combination with Taxol (chemical name: paclitaxel) followed by anthracycline chemotherapy
  • Taxol alone followed by anthracycline chemotherapy before breast cancer surgery.

Treatment given before surgery to weaken or shrink the cancer is called neoadjuvant treatment. Neoadjuvant treatment often is recommended when the breast cancer is large, aggressive, and/or has spread beyond the breast to surrounding tissue.

Of the 71 women getting the experimental regimen of veliparib and carboplatin before surgery:

  • 38 were diagnosed with triple-negative breast cancer
  • 33 were diagnosed with hormone-receptor-positive and HER2-negative breast cancer

There were 44 women diagnosed with HER2-negative breast cancer who got Taxol alone in the study.

After chemotherapy, the women had surgery to remove the breast cancer. A pathologist examined the removed tissue to see if there were signs of cancer cell activity. One way doctors judge the effectiveness of treatment given before surgery is to look at the tissue removed during surgery to see if any active cancer cells are present. If no active cancer cells are there, doctors call it a “pathologic complete response.” Many doctors believe that a pathologic complete response to neoadjuvant treatment means the cancer is less likely to come back.

In addition to looking at whether veliparib and carboplatin helped treat breast cancer before surgery, the I-SPY 2 study also was interesting because it used a new and different type of study design. The researchers used what they call an “adaptive algorithm” to see which types of breast cancer responded the best to the different regimens as the study went on. In other words, the study saw how different types of breast cancer responded to the treatments and then assigned more women diagnosed with cancers likely to respond to the treatment to that treatment arm.

When a treatment arm added enough people, that treatment “graduated” to a larger, later phase trial. The goal of the study’s design is to figure out more quickly which types of breast cancer respond to experimental treatments and then get the treatments approved and to market more quickly and efficiently.

These first results from the I-SPY 2 trial suggest that the combination of veliparib plus carboplatin and Taxol followed by standard chemotherapy before surgery is better than Taxol and standard chemotherapy alone for triple-negative breast cancer. This was based on the pathologic complete response rates:

  • 52% of women diagnosed with triple-negative breast cancer had a pathologic complete response to the veliparib-carboplatin-Taxol-anthracycline chemotherapy combination
  • 26% of women diagnosed with triple-negative breast cancer had a pathologic complete response to the Taxol-anthracycline chemotherapy regimen

For women diagnosed with HER2-negative, hormone-receptor-positive cancer, the pathologic complete response rates were:

  • 33% for women getting the veliparib-carboplatin-Taxol-anthracycline chemotherapy combination
  • 22% for women getting the Taxol-anthracycline chemotherapy regimen

Based on these positive results, the researchers recommended that the veliparib-carboplatin-Taxol-anthracycline regimen before surgery for triple-negative breast cancer be put into a phase III trial. Phase III trials compare the safety and effectiveness of a new treatment to the current standard of care. Phase III trials are large and are the last step a new treatment goes through before the FDA considers approving it for general use.

If you’ve been diagnosed with triple-negative breast cancer and are planning your treatment before surgery, you might want to talk to your doctor about this study. Ask your doctor if neoadjuvant chemotherapy makes sense for you based on your unique situation. If you’re willing to participate in a clinical trial, you may have the option of being treated with the veliparib-carboplatin-Taxol-anthracycline chemotherapy regimen. Talk to your doctor about clinical trials that might be a good fit for you. You can visit the Breastcancer.org Clinical Trials pages for more information.

And stay tuned to Breastcancer.org’s Research News for the latest information on treatments for triple-negative breast cancer.

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