Two new studies presented at the annual CTRC-AACR San Antonio Breast Cancer Symposium have potentially good news for the treatment of certain types of breast cancer. In the first, a drug (everolimus) given to women with hormone sensitive breast cancer that had experienced resistance to hormone therapy led to a longer time before the disease progressed. In the second study, a new drug (pertuzumab) added to established chemotherapy treatment for women with HER-2 positive breast cancer also led to significant delays in disease progression. We asked Len Lichtenfeld, M.D., the ACS’s deputy chief medical officer, what he thought of the news.
“These two studies demonstrate how our increasing understanding of the underlying mechanisms of cancer cells can be used to improve the treatments we can offer patients if their breast cancer returns.
“In the first clinical trial, called BOLERO-2, investigators used two established cancer drugs to increase the time it took metastatic breast cancer to progress. In that trial, women with recurrent breast cancer that was hormonally sensitive and who became resistant to hormone therapy and had failed prior treatment with hormone-blocking drugs were assigned to two groups. One group continued hormone-related treatment with a different hormone-blocking drug alone (exemestane) and another group received that same hormone-blocking drug along with a drug (everolimus) that effectively “turned off” the hormone resistance that led to the progressing disease in the first place. The results were significant, with the women receiving the drug combination having a much longer time to disease progression compared to the group that received the hormone-blocking drug alone.
“What is exciting about this trial is that the combination was based on laboratory and clinical evidence that this new approach might provide benefit for patients. Everolimus has not been considered a mainstay of breast cancer treatment previously, and research showed that it had the capacity to “reverse” hormone resistance. This study suggests that researchers could indeed produce remarkable results by rationally designing a treatment approach based on science where the hormone resistance was turned off and allowed a different hormone therapy to effectively treat the disease.
“In the other trial—dubbed CLEOPATRA—a new drug (pertuzumab) designed to block the HER-2 pathway (which is
foundover-expressed in about 30% of breast cancers, and signals a more difficult prognosis) was added to more established chemotherapy with docetaxel and trastuzumab (a mainstay of treatment for women with HER-2 positive breast cancer which also blocks the same HER-2 pathway, but through a different mechanism) again found significant delays in disease progression with the addition of pertuzumab.
“In this study, adding the pertuzumab effectively improved the ability of the targeted therapy drugs (trastuzumab and pertuzumab) to block one of the pathways on which the breast cancer cells relied for their own survival. By understanding how cancer cells work, and which pathways we can target to block the cells’ growth, we can impact the lives of patients in ways never before possible. In this case, two drugs targeting the same pathway through different mechanisms significantly increased the time it took for the breast cancer to progress.
“Together, these studies show us that through our understanding of the basic biology of cancer, we are now able to target our treatments in novel ways that were not possible previously. These studies demonstrate—in different ways—that our understanding of the basic mechanisms of cancer cells and our ability to create new drugs and new combinations of drugs are moving us closer to an era when cancer will become a more chronic disease, with exciting new treatment options available for our patients and their doctors.”