The medicine BSI-201 given in combination with chemotherapy lengthened survival in women with triple-negative metastatic breast cancer compared to those who received chemotherapy alone.
The phase II study, presented during the plenary session of the 2009 annual meeting of the American Society of Clinical Oncology, introduced doctors to poly ADP-ribose polymerase (PARP) inhibitors, a new class of treatments for cancer. These new medicines are believed to affect an enzyme that repairs DNA damage in cells and to enhance the effects of chemotherapy.
These findings will not immediately impact treatment options, but they represent an exciting potential new avenue for treating triple-negative and hereditary breast cancers. Meeting attendees consider the finding one of the most exciting in years and believe PARP inhibitors also may prove useful against ovarian and other cancers.
About Triple-Negative Breast Cancer
After a breast cancer diagnosis, a surgeon removes a piece of tumor and tests it for the presence of two hormone receptors—the estrogen and progesterone receptors—and extra copies of a gene, HER2 (human epidermal growth factor receptor 2), that increases the aggressiveness of a breast cancer. When a tumor tests negative for all three of these substances, it is classified as triple-negative breast cancer (TNBC). These cancers do not benefit from many available treatments that target hormones or HER2. As a result, researchers consider TNBC a hard-to-treat, aggressive cancer, for which chemotherapy is the main treatment option.
About PARP Inhibitors
Previous research has shown chemotherapy is the most effective treatment available for triple-negative disease, which occurs in 15 percent to 20 percent of breast cancer diagnoses.
Chemotherapy works on breast cancer cells by damaging the cells’ DNA, eventually killing the cells. All cells contain DNA, a set of directions that tell them when and how to grow and when to stop growing. But both healthy cells and cancer cells have the power to repair damage to their DNA. This powerful ability means that sometimes chemotherapy stops working because the cancer cell repairs itself before the medicine can kill it.
The medicine involved in this study, a new class of anticancer agents known as PARP inhibitors, blocks enzymes in the cancer cells that help them repair their damaged DNA. When cancer cells cannot repair their DNA after treatment with chemotherapy (or radiation therapy, which was not included in this clinical trial), the cells eventually die. Researchers are studying a variety of PARP inhibitors; the one in this study, BSI-201, is delivered intravenously (by vein).
Of the 116 women who participated in this clinical trial, 62 were randomly assigned to receive chemotherapy alone (the standard treatment), and 61 were randomly assigned to receive chemotherapy plus injections of the PARP inhibitor in three-week cycles (combination therapy). The combination chemotherapy given was gemcitabline (brand name: Gemzar) and carboplatin (brand name: Paraplatin), a standard regimen for metastatic breast cancer that grows despite treatment with other chemotherapy medicines.
Participants had measurable disease (cancer large enough for researchers to measure it to see whether it gets smaller with treatment) and up to two previous chemotherapy regimens for metastatic triple-negative breast cancer.
Participants were "restaged" every two cycles, meaning doctors measured the size of tumors to evaluate the effectiveness of the treatment. The goals of this research were to see if the study medicine would shrink breast tumors and impact survival rates, as well as to gather additional data about safety and side effects.
Overall, 62 percent of participants who received the PARP inhibitor in combination with chemotherapy benefited from the treatment (meaning the tumors either shrunk or did not grow for at least six months) versus 21 percent of those who received chemotherapy alone. A complete or partial tumor reduction was seen in 48 percent of women who received the combination therapy. People who received chemotherapy alone had a complete or partial tumor reduction rate of 16 percent.
Survival rates also were higher among women in the combination therapy group—with a progression-free survival (time without the cancer growing) of 6.9 months and overall survival (time lived after starting treatment) of 9.2 months, compared with 3.3 and 5.7 months, respectively, for women in the chemotherapy-alone group.
Researchers also found that side effects of the treatment, which included fatigue, nausea, vomiting, nerve damage, and diarrhea, were controllable and not life-threatening. Participants who received chemotherapy alone had side effects similar to those who received the PARP inhibitor plus chemotherapy.
Based on these early, promising results, researchers will begin a phase III trial of this new medication in metastatic TNBC in summer 2009. LBBC will bring you information about this study on our clinical trials page.
What Does This Study Mean for Me?
PARP inhibitors have the potential to be a new breakthrough in the treatment of breast cancer, and research in this emerging field continues. Although medical researchers are excited about these promising study results, PARP inhibitors must be taken by more women in clinical trials before the treatment can become a standard of care.
If you have the type of breast cancer studied in this clinical trial, you may wish to consider participating in one of the open or upcoming studies. Talk to your healthcare provider about the risks and benefits of joining such a study. You also may wish to read our helpful publication, Understanding Treatment Options for Advanced Breast Cancer, which you can order or download for free at our Marketplace.
J. O’Shaughnessy et al. Efficacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin (G/C) in patients with metastatic, triple-negative breast cancer (TNBC): Results of a randomized phase II trial. Presented at the 2009 Annual Meeting of the American Society of Clinical Oncology. Abstract 3.