ALEXANDRIA, Va. — The American Society of Clinical Oncology (ASCO) has been awarded $11 million in research funding by the Patient-Centered Outcomes Research Institute (PCORI) to study dosing strategies of oral CDK4/6 inhibitors in older adults living with metastatic breast cancer. The study aims to address a critical evidence gap in the treatment of this disease: dose optimization and individualization. Despite breast cancer being more prevalent in people age 65 or older, few from this age group, particularly those above 75, are included in CDK4/6 inhibitor clinical trials. 

“We are incredibly grateful to PCORI for recognizing the value of our research and providing us with this award to help improve outcomes, including improving tolerability and staying on treatment longer, for older adults with breast cancer," said Julie R. Gralow, MD, FACP, FASCO, ASCO's Chief Medical Officer and Executive Vice President. “This clinical trial builds on ASCO’s previous work to improve dose optimization for patients with cancer, and its results will help advance cancer care and outcomes for vulnerable patient populations in real-world settings.”  

Doses for CDK4/6 inhibitors were approved similarly to chemotherapy, at the maximum tolerated dose identified in the early phase of drug development. High doses of targeted therapies, including CDK4/6 inhibitors, are not necessarily required for a strong anti-cancer effect — lower doses may be highly effective.  

Older adults living with metastatic breast cancer are often unable to maintain full FDA-approved treatment doses of CDK4/6 inhibitors, with poor tolerance leading to frequent dose reductions, treatment interruptions, and early treatment discontinuation. This in turn leads to higher morbidity and mortality compared to patients who are able to tolerate treatment. In clinical practice, 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. Since older adults are frequently underrepresented in clinical trials, there is a lack of data to guide optimal treatment strategies in this population.  

This ASCO study will investigate dosing strategies for CDK4/6 inhibitors, specifically palbociclib and ribociclib, which are used in combination with endocrine therapy for treating patients with hormone receptor-positive breast cancer. The, "Comparing Oral Drug Dosing Strategies in Older Patients with Metastatic Breast Cancer to Maximize Tolerance and Reduce Discontinuation: The CDK4/6 Inhibitor Dosing Knowledge (CDK) Study” will compare starting treatment at the full dose with decreases for side effects versus a lower initial 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 anti-cancer effect. 

The study was designed to meet patient and clinician needs, using broad eligibility criteria and a pragmatic, patient-centric trial design. It will be conducted primarily by sites that already do research with ASCO through the TAPUR (Targeted Agent and Profiling Utilization Registry) network, with an established history of successfully enrolling people with metastatic cancer in studies, including those from diverse racial and ethnic groups as well as older adults.  

“This project was selected for PCORI funding not only for its scientific merit and commitment to engaging patients and other healthcare stakeholders, but also for its conduct in real-world settings. It has the potential to answer an important question about metastatic breast cancer treatment and fill a crucial evidence gap,” said Nakela L. Cook, MD, MPH, PCORI Executive Director. “We look forward to following the study’s progress and working with ASCO to share its results.” 

The CDK study is being led by Dr. Gralow, Principal Investigator of the study; Dawn L. Hershman, MD, MS, FASCO, Herbert Irving Comprehensive Cancer Center at Columbia University and NewYork-Presbyterian; Erica L. Mayer, MD, MPH, FASCO, Dana-Farber Cancer Institute; and Janice Cowden, research patient advocate, Patient-Centered Dosing Initiative. It was selected through a highly competitive review process in which patients, caregivers and other stakeholders joined scientists to evaluate the proposals. It was selected for funding through a PCORI program designed to support research that produces results that are useful for a wide variety of patients and can be easily applied in everyday healthcare. 

ASCO’s award has been approved pending completion of a business and programmatic review by PCORI staff and issuance of a formal award contract.  

PCORI is an independent, nonprofit organization authorized by Congress in 2010. Its mission is to fund research that will provide patients, their caregivers and clinicians with the evidence-based information needed to make better informed healthcare decisions. For more information about PCORI’s funding, visit www.pcori.org.

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