Pharmacologic treatment for women with endocrine-refractory or triple-negative metastatic breast cancer (mBC) can be extremely expensive while only providing a modest benefit in extending a patient’s life or improving their quality of life. Therefore, a group of researchers sought to determine if sequence of the first to third lines would have an impact on societal cost-effectiveness of treatment. Their findings were published in the Journal of Clinical Oncology.

“In this mBC setting where multiple chemotherapy options are recommended by guidelines and share similar survival and adverse event trajectories, treatment sequencing approaches that seek to minimize costs early may help improve value of care,” explained the researchers.

Three dynamic microsimulation models of 10,000 patients each was created to determine the cost-effectiveness of certain treatment sequences for mBC. The cohorts were based on prior chemotherapy exposure. The model evaluated the cost-effectiveness of commonly used single-agent chemotherapy sequences for each cohort.

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  • Cohort 1 Patients were unexposed to taxane or anthracycline. The model found sequences of paclitaxel, capecitabine, doxorubicin or paclitaxel, doxorubicin, capecitabine resulted in lower costs and higher expected quality-adjusted life years (QALYs).
  • Cohort 2 Patients were exposed to taxane or anthracycline. The model found the sequence of carboplatin, capecitabine, eribulin resulted in the lowest cost and higher QALYs.
  • Cohort 3 Patients were exposed to taxane but not anthracycline. Sequences beginning with capecitabine and doxorubicin resulted in higher QALYs. Following capecitabine with doxorubicin in the second line is a better cost-effective option than eribulin ($1765/mo vs $8000/mo).

In this study, eribulin, the most expensive treatment and carrying a high expected adverse event burden, performed particularly poorly in the cohorts in which it was evaluated. Based on cost-effectiveness alone, it should be last in a sequence.

Improving the value of care for patients with mBC should be a priority. “Our study suggests that large incremental differences in endocrine-refractory or triple-negative mBC systemic treatment costs are not likely associated with better outcomes, which is informative for oncology value frameworks, pathway development, and policy,” the researchers noted in their report.

However, other factors should also continue to influence practice, such as open communication about adverse event risks and involving patients in shared decision making.

Study limitations included a focus on only moderate to severe adverse events measured in clinical trials. The models didn’t take into account milder adverse events that might still be meaningful to patients or the possibility that patients on different treatment regimens might react differently to multiple adverse effects. Cost assumptions and findings will also need to be reevaluated over time, since drug pricing is an inherently dynamic process.

“Our analysis addresses notable gaps in existing treatment guidelines for chemotherapy of HER2-negative breast cancer when clinical outcomes are similar and costs are quite different — representing an improvement above and beyond what existing guidelines and pathways may offer in the metastatic triple-negative or endocrine-refractory breast cancer setting,” concluded the researchers.

Disclosures: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Wheeler SB, Rotter J, Gogate A, et al. Cost-effectiveness of pharmacologic treatment options for women with endocrine-refractory or triple-negative metastatic breast cancer. J Clin Oncol. Published online September 2, 2022. doi:10.1200/JCO.21.02473