Patients with metastatic cancer, including metastatic breast cancer (MBC), are often treated with palliative intent and may receive multiple lines of therapy over many years. New, increasingly effective treatments have been developed using traditional study designs that do not always establish dose-limiting toxicities and maximum tolerated dose. The Patient-Centered Dosing Initiative (PCDI), a group of patient advocates and an advisory board of medical oncologists, asserts that for precision medicine to realize its full potential, patient history, environment, and lifestyle must be considered. To better understand the experiences and perspectives of patients with MBC regarding selection of initial dose and dose optimization, the PCDI conducted an online, self-administered survey of more than 1,000 patients with MBC receiving treatment in the palliative setting. The survey was intended to determine the magnitude of treatment-related side effects.
Most survey respondents reported at least 1 self-defined negative treatment-related side effect, including fatigue, nausea, low blood counts, diarrhea, and neuropathy. As a result of treatment-related side effects, 20% visited the emergency room/hospital and 43% reported missing a scheduled treatment. Quality of life improved for the majority of patients who were given a reduced dose, substantiating the rationale for leveraging dose reduction as a highly effective mechanism for side-effect palliation. Most patients reported relief with dose reduction and the majority responded that they would be willing to discuss drug dosing options with their physicians on the basis of their unique characteristics, such as comorbidities, body mass index, reactions to previous therapies, and personal goals/wishes.
High level
The standard method of dose identification and administration in prospective study designs must evolve to better define optimal dose selection and reduce treatment-related side effects. In alignment with the US Food and Drug Administration’s Project Optimus, it is recommended that clinical trial researchers select 1 or more doses in early-phase clinical trials for further study to determine the optimal dose for maximizing efficacy, safety, and tolerability of new oncology treatments.
Ground level
With new treatments enabling patients to live longer, flexible personalized dosing strategies are becoming increasingly important to preserve patients’ quality of life and continually balance efficacy and toxicity throughout treatment. Clinicians should be aware of patients’ strong interest in discussions of optimal dosing of systemic therapy to address their needs and preferences. Approximately 1 out of 5 patients in the survey had been unaware that dose adjustments could help alleviate side effects, highlighting the importance of patient education and ongoing dialogue regarding dose selection. Dose reductions as a method to address treatment-related side effects should be discussed with patients, along with reassurance that a higher dose is not always more effective than a lower dose.
