Clinical trials in older patients with cancer – typical challenges, possible solutions, and a paradigm of study design in breast cancer

Background and purpose: While the prevalence of older breast cancer patients is rapidly increasing, these patients are greatly underrepresented in clinical trials. We discuss barriers to recruitment of older patients to clinical trials and propose solutions on how to mitigate these challenges and design optimal clinical trials through the paradigm of IMPORTANT trial. Patients and methods: This is a narrative review of the current literature evaluating barriers to including older breast cancer patients in clinical trials and how mitigating strategies can be implemented in a pragmatic clinical trial. Results: The recognized barriers can be roughly divided into trial design-related (e.g. the adoption of strict inclusion criteria, the lack of pre-specified age-specific analysis), patient-related (e.g. lack of knowledge, valuation of the quality-of-life instead of survival, transportation issues), or physician-related (e.g. concern for toxicity). Several strategies to mitigate barriers have been identified and should be considered when designing a clinical trial dedicated to older patients with cancer. The pragmatic, de-centralized IMPORTANT trial focusing on dose optimization of CDK4/6-inhibitors in older breast cancer patients is a paradigm of a study design where different mitigating strategies have been adopted. Interpretation: Because of the existing barriers, older adults in clinical trials are considerably healthier than the average older patients treated in clinical practice. Thus, the study results cannot be generalized to the older population seen in daily clinical practice. Broader inclusion/exclusion criteria, offering tele-health visits, and inclusion of patient-reported, instead of physician-reported outcomes may increase older patient participation in clinical trials.