For metastatic breast cancer that is endocrine-refractory or triple-negative, there are multiple chemotherapy options, but little guidance on which ones to use first or how to optimize sequencing of trying various regimens. "Because the economic and quality-of-life burden associated with these ongoing treatments may be different, we were interested in exploring whether optimal chemotherapy sequences could be identified considering factors important to patients, such as drug costs, productivity losses, and side effects," noted Stephanie Wheeler, PhD, Professor of Health Policy and Management at Gillings School of Global Public Health at University of North Carolina at Chapel Hill and Associate Director of Community Outreach and Engagement at UNC's Lineberger Comprehensive Cancer Center.
That's the analysis she and her colleagues conducted with the results published in the Journal of Clinical Oncology (2022; doi: 10.1200/JCO.21.02473). The researchers developed three different computer models to predict how a hypothetical set of 10,000 patients with specific types of metastatic breast cancer would respond to various sequences and types of chemotherapy. For the models, patients' cancers were either no longer responding to hormone therapies or were triple-negative breast cancer. Here's what Wheeler said about her group's data and their ongoing work to optimize the value and minimize societal and patient costs of cancer care.
1 How did you set up this analysis to estimate cost-effectiveness of various first- to third-line sequences of single-agent chemotherapy regimens for people with endocrine-refractory or triple-negative metastatic breast cancer?
"With expert oncologist input, we modeled common chemotherapeutic regimens for three different metastatic patient cohorts, based upon prior treatment exposure-people who had previously received a taxane and an anthracycline, people who had received neither, and people who received a taxane but not anthracycline. For each cohort, we estimated total quality-adjusted life years, considering survival expectancy and side effects from treatment, as well as costs, considering both medical costs and non-medical, productivity costs, based upon published trials and other literature.
"Cost-effectiveness analyses then compared treatment sequences within each cohort and yielded findings that suggested that starting treatment sequences with the least expensive chemotherapy drugs was cost-effective or cost-saving, even in some cases, without compromising survival or quality of life. These results were robust in sensitivity analyses.
"In most cases, our analyses actually show that starting sequences with the cheapest chemotherapies confers the largest benefits clinically in terms of quality-adjusted life years. Specifically, our results suggest that for taxane- and anthracycline-exposed patients, treatment with [carboplatin], followed by [capecitabine], followed by eribulin corresponds to the highest expected quality-adjusted life years gain and lowest costs. For taxane- and anthracycline-unexposed patients, treatment with [paclitaxel], followed by [carboplatin], followed by [doxorubicin] corresponds to the highest expected quality-adjusted life years gain and lowest costs. And for taxane-exposed/anthracycline-naive patients, treatment sequences beginning with [capecitabine], or [doxorubicin], followed by eribulin corresponds to the highest expected quality adjusted life years gain and lowest costs."
2 What are the implications of these findings?
"We found that there is little value in starting chemotherapy sequences in this setting with more expensive medications because survival and quality-of-life profiles were similar across treatment sequences over time; therefore, treatment sequences that minimize costs early should be prioritized.
"The implications are clear. In this metastatic setting where multiple chemotherapy options are recommended by guidelines and share similar survival and adverse effect trajectories, treatment sequences that minimize costs early may help improve the value of care, not only for society, but also for individual patients.
"As the cost of cancer drugs continues to skyrocket and as patients continue to be devastated by the cost of their illness, providers should be empowered to choose clinically equivalent therapeutic alternatives that are less expensive and less financially burdensome to patients. These data provide quantified evidence that can inform those decisions and can reduce patient financial toxicity while maintaining high-quality care."
3 What's the next step of your work?
"The current study attempts to provide economic evaluation evidence that can motivate providers and policymakers to choose higher-value treatments to address patient-level financial toxicity and societal drug costs. We know that this is a necessary but insufficient solution to the problem and that other solutions are also required, including major health policy payment reforms and direct patient-facing interventions.
"In the latter space, we are currently in the process of scaling up and studying the implementation of a financial navigation intervention we developed at UNC that directly assists patients with financial literacy, health insurance and social resource support, and financial case management to build patient and caregiver capacity to manage the costs of their cancer care. This work is underway as an NCI-supported clinical trial in nine rural and non-rural oncology sites in North Carolina.
"Our analysis addresses notable gaps in existing treatment guidelines in the metastatic triple-negative or endocrine-refractory breast cancer setting when clinical outcomes are similar and costs are quite different. These data should hopefully motivate providers to choose lower-priced, equally effective chemotherapy options in this setting."