Metastatic breast cancer occurs when cancer cells spread outside the breast and local tissues. It is considered incurable, but highly treatable. People with metastatic breast cancer may live for many years on treatment with good quality of life. Over 168,000 people in the United States were estimated to be living with metastatic breast cancer in 2020. The majority of breast cancers are hormone receptor positive, meaning they contain proteins that attach to the hormones estrogen and progesterone. These cancers can be treated with drugs called hormone (or endocrine) therapy that lower or block estrogen. CDK4/6 inhibitors are newer drugs that are used to treat breast cancer in combination with hormone therapy.
Higher doses of traditional anticancer chemotherapy drugs lead to greater treatment success or “anticancer effect.” Therefore, the dose approved by the U.S. Food and Drug Administration for chemotherapy drugs is based on the maximum dose patients can tolerate. CDK4/6 inhibitors are known as targeted therapies. They work differently from chemotherapy drugs by targeting specific proteins involved in cancer growth. Doses for CDK4/6 inhibitors were approved similarly to chemotherapy, at the maximum amount that people can tolerate. Studies have shown, however, that high doses of targeted therapies are not necessarily required for a strong anticancer effect. A lower dose may be highly effective.
CDK4/6 inhibitors cause side effects, such as fatigue and lowering number of white blood cells. Side effects increase at higher doses. Many people must pause, reduce or discontinue CDK4/6 inhibitors because of side effects. This is particularly true for people 65 years and over. People who experience intolerable side effects may stop therapy sooner, even if the cancer is responding. Information from clinical practice shows that physicians start some people at lower doses, especially those who are older or frail. Some people are not prescribed CDK4/6 inhibitors at all due to concerns about tolerability. Medical guidelines recommend CDK4/6 inhibitors be combined with endocrine therapy in hormone positive metastatic breast cancer regardless of age.
This study focuses on older patients (age 65 years and older) with hormone receptor positive metastatic breast cancer. While most people with breast cancer are age 65 years and older, clinical trials of CDK4/6 inhibitors included small numbers in this age group. Patients and clinicians need more information about dose, toxicity and effectiveness in these patients.
The primary purpose of this study is to compare dosing strategies for two CDK4/6 inhibitors (palbociclib and ribociclib). Participants must have a plan to start treatment with a CDK4/6 inhibitor in combination with endocrine therapy. The study will compare starting treatment at the full dose with decreases for side effects versus a lower dose with increases if tolerated. The study will measure how long the participant stays on treatment with the CDK4/6 inhibitor. Staying on therapy longer can increase the possibility of a significant and prolonged anticancer effect. The study will look at side effects and quality of life reported directly by participants. It will study treatment interruptions, doses received, days a patient cannot take the drug and how well the drug is working. It will also evaluate use of health services, including hospital visits and wasted pills with dose changes.
The study will be conducted by sites that already do research with the American Society of Clinical Oncology (ASCO). These sites have a history of successfully enrolling people with metastatic cancer in studies. ASCO designs studies that meet patient and clinician needs, using broad eligibility criteria (with very few reasons that patients cannot enroll). This makes it easy for doctors and patients to participate. ASCO research sites focus on enrolling people who are commonly not included in clinical trials, including those representing racial and ethnic minorities and older patients. The advisory group for this study includes patient partners (including patients living with metastatic breast cancer) as well as breast cancer researchers and clinicians.
This study will generate evidence that will help patients and clinicians make informed, personal decisions about their cancer treatment. The research team aims to help people with metastatic breast cancer get the most treatment benefit for as long as possible. This includes decreasing side effects for the best quality of life.
*All proposed projects, including requested budgets and project periods, are approved subject to a programmatic and budget review by PCORI staff and the negotiation of a formal award contract.