E-Newsletter - October 2024
Spotlight on Alliance Trials

ALLIANCE features SIX trials during NATIONAL Breast Cancer AWARENESS MONTH

Breast cancer is the second most common cancer in women after skin cancer, according to the National Cancer Institute. It affects 2.3 million women worldwide. More than 270,000 women are diagnosed with breast cancer each year in the U.S., and about 42,000 will die from the disease, according to the Centers for Disease Control and Prevention. However, according to the American Cancer Society, through early detection, the 5-year relative survival rate for localized cancer that hasn't spread is 90%. It is also estimated that this year, about 30% of all new women cancer diagnoses will be breast cancer. Sixty-five percent of breast cancer cases are diagnosed at a stage where there is no sign that the cancer has spread outside of the breast, for which the 5-year relative survival rate is 99%. What's more, there are nearly 4 million breast cancer survivors in the U.S. Mammograms can detect breast cancer early, possibly before it has spread.

Currently, Alliance has five active trials in its portfolio that have a focus on breast cancer.

• A011801 (COMPASS HER2 RD/Breast Cancer)
• A012103 (Early-stage Triple Negative Breast Cancer)
• A071701 (Genomically-guided Treatment in Brain Metastases)
• A191901 (Optimizing Endocrine Therapy)
• A211801 (BRCA-P Study: BRCA1 Germline Mutation)
• A222101 (Preventing Paclitaxel-associated Neuropathy)

Alliance A011801 (COMPASS HER2 RD/Breast Cancer)

Ciara C. O'Sullivan, MB, BCh, BAO, of the Mayo Clinic, leads Alliance A011801 (The CompassHER2 trials (Comprehensive use of pathologic response assessment to optimize therapy in HER2-positive breast cancer) CompassHER2 residual disease (RD), a double-blinded, phase III randomized trial of T-DM1 compared with T-DM1 and tucatinib). This phase III trial studies how well trastuzumab emtansine (T-DM1) and tucatinib work in preventing breast cancer from coming back (relapsing) in patients with high risk, HER2 positive breast cancer. T-DM1 is a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called DM1. Trastuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors, and delivers DM1 to kill them. Tucatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving T-DM1 and tucatinib may work better in preventing breast cancer from relapsing in patients with HER2 positive breast cancer compared to T-DM1 alone. The trial opened on January 6, 2021. Learn more: https://bit.ly/Alliance-A011801 | Alliance Member Site

Alliance A012103 (Early-stage Triple Negative Breast Cancer)

Sara Tolaney, MD, of Dana-Farber Cancer Institute, leads Alliance A012103 (OptimICE-pCR: De-escalation of therapy in early-stage TNBC patients who achieve pCR after neoadjuvant chemotherapy with checkpoint inhibitor therapy). This phase III trial compares the effect of pembrolizumab to observation for the treatment of patients with early-stage triple-negative breast cancer who achieved a pathologic complete response after preoperative chemotherapy in combination with pembrolizumab. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial may help researchers determine if observation will result in the same risk of cancer coming back as pembrolizumab after surgery in triple-negative breast cancer patients who achieve pathologic complete response after preoperative chemotherapy with pembrolizumab. The trial opened on May 10, 2023. Learn more: https://bit.ly/Alliance-A012103 | Alliance Member Site

Alliance A071701 (Genomically-guided Treatment in Brain Metastases)

Priscilla Brastianos, MD, of Massachusetts General Hospital, leads Alliance A071701 (Genomically-guided treatment trial in brain metastases). This phase II trial looks at how well genetic testing works in guiding treatment for patients with solid tumors that have spread to the brain. Several genes have been found to be altered or mutated in brain metastases such as NTRK, ROS1, CDK or PI3K. Medications that target these genes such as abemaciclib, GDC-0084, and entrectinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Genetic testing may help doctors tailor treatment for each mutation. The trial opened on August 15, 2019. Learn more: http://bit.ly/AllianceA071701 | Alliance Member Site

Alliance A191901 (Optimizing Endocrine Therapy)

Katherine E. Reeder-Hayes, MD, MBA, MSc, of University of North Carolina at Chapel Hill, leads Alliance A191901 (Optimizing endocrine therapy through motivational interviewing and text interventions). This phase III trial compares an additional support program, using text message reminders and/or telephone-based counseling, with usual care in making sure patients with breast cancer take their endocrine therapy medication as prescribed. Poor medication adherence has been shown to be a serious barrier to effective treatment for patients with breast cancer that is hormone receptor positive. Adding text message reminders and/or telephone-based counseling to usual care may increase the number of days that patients take their endocrine therapy medication as prescribed. The trial opened on December 10, 2020. Learn more: https://bit.ly/Alliance-A191901 | Alliance Member Site

Alliance A211801 (BRCA-P Study: BRCA1 Germline Mutation)

Judy E. Garber, MD, MPH, of Dana-Farber Cancer Institute, leads Alliance A211801 (BRCA-P: A randomized, double-blind, placebo-controlled, multi-center, international phase 3 study to determine the preventive effect of denosumab on breast cancer in women carrying a BRCA1 germline mutation). This phase III trial that compares denosumab to placebo for the prevention of breast cancer in women with a BRCA1 germline mutation. A germline mutation is an inherited gene change which, in the BRCA1 gene, is associated with an increased risk of breast and other cancers. Denosumab is a monoclonal antibody that is used to treat bone loss in order to reduce the risk of bone fractures in healthy people, and to reduce new bone growths in cancer patients whose cancer has spread to their bones. Research has shown that denosumab may also reduce the risk of developing breast cancer in women carrying a BRCA1 germline mutation. The trial opened on February 23, 2022. Learn more: https://bit.ly/Alliance-A211801 | Alliance Member Site

Alliance A222101 (Preventing Paclitaxel-associated Neuropathy)
Elizabeth Cathcart-Rake, MD, of Mayo Clinic, leads Alliance A222101 (An early phase and phase II clinical trial to evaluate ganglioside-monosialic acid (GM1) for preventing paclitaxel-associated neuropathy). This phase II trial tests the safety, side effects, and best dose of monosialotetrahexosylganglioside (GM1) and whether it works in reducing or preventing chemotherapy-induced peripheral neuropathy (CIPN) in patients with breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) who are receiving treatment with paclitaxel. Chemotherapy drugs, such as paclitaxel, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Exposure to chemotherapy drugs like paclitaxel may cause a side effect called CIPN, which is a condition of weakness, numbness, and pain from nerve damage (usually in the hands and feet). GM1 is a part of the body's natural system that insulates nerves and helps to protect nerves from damage. Giving GM1 may help reduce or prevent CIPN in breast cancer patients receiving treatment with paclitaxel. The trial opened on May 31, 2023. Learn more: https://bit.ly/Alliance-A222101 | Alliance Member Site