by Sue Friedman
Great progress has been made since the identification of the BRCA1 and BRCA2 genes and their link to causing breast, ovarian, pancreatic and other cancers. Over the last two decades, researchers have studied how BRCA mutations cause cancer in an effort to develop new treatments. In December 2014, Lynparza, (olaparib), a type of drug known as a PARP inhibitor, was approved as the first targeted agent to treat BRCA-associated cancers for women who have progressed after three prior lines of therapy.
Researchers are now using this knowledge to test olaparib in people with BRCA mutations who have been diagnosed with breast cancer. Until now the main focus has been studying PARP inhibitors in people with advanced or metastatic cancer. The OlympiA trial is the first major study to test a targeted therapy for people with BRCA mutation-associated breast cancer in the adjuvant setting (after surgery) for people with earlier-stage (stage 2 or stage 3) cancers. You can learn more about this study by watching this webinar by Dr. Charles Geyer, one of the principle investigators for the study.
BRCA 1/2 Mutations
Approximately 5% of breast cancers are associated with inherited mutations in the BRCA1 or BRCA2 genes. Women with triple-negative breast cancer, breast cancer diagnosed before age 50, a strong family history of cancer, men with breast cancer, and people who are of Eastern European Jewish descent are more likely to have a BRCA mutation. The majority of breast cancers that develop in people with BRCA1 mutations are triple-negative breast cancers (70%), while those with mutations in the BRCA2 gene are more likely to develop estrogen receptor–positive (also known as ER+) breast cancer (70%). Until recently, very few clinical trials have evaluated potential new therapies specifically in patients with BRCA mutations; most of the studies in breast cancer have focused on women with metastatic disease. OlympiA is the first PARP inhibitor for earlier-stage breast cancer.
Olaparib Clinical Trials in Breast Cancer
Several PARP inhibitors are in development, and the FDA approved olaparib in December 2014 to treat women with advanced ovarian cancer with deleterious germline mutations in BRCA1 or BRCA2. Olaparib has also shown promise in patients with BRCA mutations who have recurrent metastatic breast cancer, although not enough data yet exists to seek approval from the FDA. Studies of PARP inhibitors in metastatic breast cancer are ongoing.
OlympiA is a phase III clinical trial studying the safety and effectiveness of olaparib for women with a BRCA mutation after they have completed standard therapy. The study is open to patients who have been diagnosed with stage 2 or stage 3 breast cancer who are considered curable but at high risk for recurrence. OlympiA participants are required to complete all standard treatments, including chemotherapy and surgery and, if needed, radiation therapy. Patients can receive either neoadjuvant or adjuvant chemotherapy. After chemotherapy has been completed, participants who enroll in OlympiA will be randomized to receive either olaparib or a placebo for a year after standard treatment. Because the study begins after chemotherapy ends—a time when patients do not typically receive additional therapy—comparing Lynparza to a placebo is appropriate. Patients will be followed closely for disease recurrence and new cancers for approximately 10 years to determine the efficacy of adjuvant treatment with olaparib on invasive disease-free survival.
The trial is actively recruiting eligible women and men with an inherited BRCA1 or BRCA2 gene mutation who have been diagnosed with triple-negative breast cancer or hormone sensitive/Her2 negative breast cancer. Since only women and men with BRCA mutations can participate, recruiting the 1,500 patients required to complete the study will be challenging. But this effort is necessary before these new drugs can be used more widely for people with BRCA-associated breast cancer. So it’s important to spread the word about the study among patients with BRCA mutations who are newly diagnosed with, or in treatment for breast cancer. The trial is being conducted in 23 countries, including 100s of sites in the United States. For information regarding US sites contact NRG Oncology Clinical Coordinating Department 1-800-477-7227.
The only path to improving health outcomes among people with hereditary cancer risk is through completion of research studies and clinical trials.FORCE has a commitment to promoting research that will provide better options for our community. We testified to the FDA in favor of Lynparza approval in ovarian cancer. Progress takes research and research takes patients! The move to study PARP inhibitors in earlier-stage, high-risk cancers indicates a large and important step towards improving care and outcomes for people with hereditary cancers. If this study is successful and shows survival benefit for patients, it could open up access to targeted therapy for thousands of people with breast cancer due to a BRCA mutation. It also provides a path for more targeted therapy clinical trials for hereditary cancers. I want to encourage the entire community to join this global effort and reach out to educate other patients who meet the eligibility criteria about the landmark OlympiA study. For information regarding US sites contact NRG Oncology Clinical Coordinating Department 1-800-477-7227. Visit our clinical research page for other prevention, detection, and treatment research studies enrolling patients.
See this quick-guide for exclusion and inclusion criteria.