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Treatment of metastatic breast cancer (MBC) has improved dramatically with the advent of targeted therapies, but the method of dose selection hasn't always kept up with the times, noted authors of a study in .

Dose selection in clinical trials is still based on the decades-old "more-is-better" paradigm from the era of cytotoxic chemotherapy, and patient quality-of-life often suffers as a result, explained Aditya Bardia, MD, MPH, of UCLA Health Jonsson Comprehensive Cancer Center in Los Angeles, and colleagues.

They surveyed 1,221 MBC patients via the (PCDI), a patient advocacy group. "To our knowledge, this is the first survey to highlight the nuances of the experience of a large volume of patients with MBC concerning their treatment, while delving into their viewpoints about dose optimization based upon unique individual characteristics," the researchers wrote.

The majority of patients (86%) reported at least one significant treatment-related side effect. Of these, 20% visited a hospital or emergency room as a result, and 43% missed at least one treatment. Of those given a dose reduction for their side effect, 83% reported relief.

Furthermore, more than half of patients (53%) said they didn't believe a higher dose was always more effective, and most (92%) said they would be willing to discuss flexible dosing options with their physician to improve quality of life.

In the following interview, study co-authors Janice Kim, MD, of Massachusetts General Hospital in Boston, and Julia Maues, MA, a breast cancer survivor, patient advocate, and founding member of the PCDI, elaborated on the findings, as well as ongoing efforts to optimize dosing for patients.

What are the implications for clinical practice?

Kim: Given the advent of many more effective anti-cancer therapies, people with metastatic breast cancer are living longer and are on therapies longer. Thus, not unexpectedly, our study showed that the majority of people surveyed experienced at least one self-defined bad side-effect. Importantly, patients expressed interest in discussing approved drug dosing options based upon their unique characteristics such as reactions to previous therapies and personal goals/wishes.

This serves as a strong reminder to medical oncologists such as myself to constantly reassess and discuss with patients the dosages of the treatments they are on. While we strive to shrink and/or control metastatic breast cancer for as long as possible, usually by prescribing cancer treatments at the FDA-recommended starting dose, we must also do our best to tailor treatments to the individuals in front of us, because the goal of treatment is not only to prolong life but also to preserve quality of life.

Do you have advice for how best to discuss flexible dosing options with patients?

Kim: When considering flexible dosing options, an individualized approach is critical alongside in-depth discussions of the risks and benefits. Even if ongoing early-phase clinical trials identify an optimal biological dose [OBD] of a drug, that dose may not be the OBD for the patient in front of you and their cancer given varying subtypes and genomic backgrounds.

Thus, it is important that we regularly revisit these nuances of treatment with patients and base decisions about dose on important factors such as the tempo of their disease, their side effects to medications, and their goals of care.

Maues: We encourage clinicians to ask about side effects often and in different ways. Know that patients, especially metastatic and female patients, are often stoic and afraid that "complaining" about side effects will mean being taken off a drug that is working, so they push through as their quality of life plummets.

What is the Patient-Centered Dosing Initiative?

Maues: is a patient-led effort, with the support of a medical advisory board of world-renowned oncologists, advocating for a paradigm shift in determining cancer drug dosing strategies. Traditional oncology drug dosing practices relied on identifying the maximum tolerated dose through phase I dose-escalation methodology. This older approach is not universally applicable, especially for newer treatments like targeted therapies and immunotherapies.

PCDI challenges this "more is better" ethos, particularly as we are living with metastatic breast cancer ourselves, as we not only seek longevity but also a high quality of life since most metastatic breast cancer patients stay on treatment for the rest of their lives.

Your paper mentioned some FDA efforts to improve dose selection in clinical trials. What are these?

Kim: is one of the pivotal initiatives of the FDA's Oncology Center of Excellence [OCE] that encourages industry to study several doses of a drug in early-phase clinical trials with the goals of maximizing efficacy, safety, and tolerability. In tandem, the OCE's is aimed at updating labeling information for previously approved oncology drugs based upon published clinical studies and post-marketing experience. These two initiatives will hopefully ensure that patients will be prescribed not only efficacious but also tolerable doses of medications.

PCDI previously surveyed oncologists on this topic. What did that survey find?

Maues: Our conclusion to that states: "Treatment-related side effects are prevalent among patients with MBC, resulting in missed treatments and acute care visits. To help patients tolerate treatment, oncologists may decrease initial and/or subsequent doses. The majority of oncologists reject the premise that a higher dose is always superior and are willing to discuss individualized dosing with patients. Given potential improvements regarding quality of life and clinical care, dose modifications should be part of routine shared decision-making between patients and oncologists."

Some highlights of our 119 oncologist responses:

• 47% of patients reported distressing treatment-related side effects

• 15% of these visited the emergency department/hospital, and 37% missed treatment

• 74% of doctors reported improvement in patient symptoms after dose reduction

• 87% indicated they had, if appropriate, initiated treatment at lower doses

• 85% did not believe the standard dose is always more effective than a lower dose

• 97% were willing to discuss individualized dosing with patients

Read the study here and expert commentary about it here.