Patient advocate-led study reveals need for dosing reform in metastatic breast cancer
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Innovative dosing strategies are warranted to improve the well-being of individuals with metastatic breast cancer, according to a patient advocate-led study published in JCO Oncology Practice.
Most patients with metastatic breast cancer experienced at least one significant treatment-related adverse event, researchers concluded. However, most of those who received dose reductions reported improvement.
Researchers sent an anonymous online survey in August 2020 to individuals with self-reported metastatic breast cancer to determine the prevalence and extent of treatment-related adverse events. The survey also addressed patient-physician communication, strategies for alleviating adverse events, patients’ perceptions about higher vs. lower doses, and their openness to discussing alternative dosing.
The majority (86.1%) of the 1,221 patients who completed the survey reported they experienced at least one substantial treatment-related adverse event.
Most patients (97.6%) who experienced a treatment-related adverse event notified their physician and 81.7% indicated they received help from their provider.
The majority (82.6%) of the 556 patients who received dose reductions reported relief. More than half (53.3%) of survey respondents indicated they did not think a higher dose would necessarily be more effective than a lower dose, and 92.3% said they would be willing to talk with their physician about flexible dosing options to improve quality of life.
The study comes amid increased awareness about the issue of dose optimization. In 2021, the FDA’s Oncology Center of Excellence launched Project Optimus, an initiative designed to reform dose selection and optimization for cancer drugs.
“The FDA has really grabbed onto this concept,” study co-author Julia Maues, MA — a member of the Patient-Centered Dosing Initiative, which advocates for a paradigm change to cancer drug-dosing strategies — told Healio. “They know patients need better dosing, especially those with metastatic disease.”
Healio spoke with Maues — who lives with metastatic breast cancer — about the study’s findings and how they contribute to ongoing dialogue about dose optimization in oncology.
Healio: What prompted you to conduct this study?
Maues: This study stemmed from our group, the Patient-Centered Dosing Initiative, which was founded in 2019 by a group of patients living with metastatic breast cancer. The idea and main driving force behind it came from Anne Loeser, who passed away in October 2023 from metastatic breast cancer. She knew how dosing affects the quality of life of people living with metastatic breast cancer.
Healio: Why is the current approach to drug dosing potentially problematic?
Maues: Dosing is often determined through dose escalation in phase 1 clinical trials. Small groups of patients are given increasing doses of the drug until the dose level where patients can’t tolerate the side effects. That dose is considered too high, so the level before it is considered the maximum tolerated dose (MTD). The MTD is then moved to later phases of trials, where they evaluate efficacy and compare it to the standard of care. Eventually, millions of people go on to take the medication at that dose.
When you have metastatic breast cancer, you usually stay on that treatment for the rest of your life, as long as it’s working against the cancer and you can tolerate it. When we take these drugs for extensive periods, many of the side effects are cumulative. A patient might experience neuropathy that is tolerable for a while but, if they stay at that same dose for months or years, that level of neuropathy may increase and could become irreversible.
Healio: How did you conduct this study?
Maues: One of the things Anne always wanted to do was to survey patients about the side effects they were experiencing and the impact these effects were having on quality of life. Because the survey was patient led, and many of us are very well-connected in the advocacy community, the response rate was excellent.
Healio: What did you find?
Maues: We found that 86% of the patients reported experiencing at least one treatment-related side effects that they considered “bad.” Of those, 20% had to visit the emergency room due to a side effect of their medication. Another statistic that was heartbreaking was that 43% — almost half — of respondents had to miss a treatment of the drug that was saving their life because that drug was so toxic.
We asked about dose reductions, and 83% of those who had a dose reduction felt better after the reduction. Some of the most common adverse events were fatigue, nausea and low blood count.
Healio: How did the oncology community respond to your study?
Maues: We did this survey and presented the findings at the ASCO Annual Meeting in 2021. When we submitted the abstract, our aspiration was to get selected for a poster. Instead, the achievement was much larger — we got an oral presentation on the main stage of the metastatic session. Anne gave an excellent talk, and the work was very well received. Her talk was in many people’s “best of ASCO” lists and she was then invited to give several additional talks. Just 3 months after Anne spoke at ASCO, the FDA published a very impactful journal article discussing how the drugs are too toxic and patients need better dosing.
Healio: How do you think these findings will advance the progress of dose optimization efforts?
Maues: It’s already happening. The FDA has launched Project Optimus, which is their initiative for drug development to look at more than one dose in those earlier trials, and studying them for longer periods so they find the best dose. They also already have draft guidance, and people have submitted comments on better ways to find the right dose in clinical trials. We have definitely seen progress.
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For more information:
Julia Maues, MA, can be reached at julia@graspcancer.org.
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