Study Examines Cost-Effectiveness of Treatment Sequencing for HER2-Positive Breast Cancer

Targeted therapies have been shown to significantly improve the survival of patients with human epidermal growth factor 2 (HER2)-positive metastatic breast cancer. However, these therapies have also been associated with high acquisition costs. In a new study, published in Breast Cancer Research and Treatment, researchers compared the cost-effectiveness of different treatments that can be used in patients with newly diagnosed HER2-positive metastatic breast cancer.


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Recently published guidelines from the American Society of Clinical Oncology and the National Comprehensive Care Network have outlined the initial sequencing strategy of HER2-targeted agents for this patient population. The combination of trastuzumab, pertuzumab, and docetaxel (THP) is recommended as first-line therapy, followed by trastuzumab emtansine (T-DMI) upon first disease progression. Third-line therapy is lapatinib in combination with either capecitabine or trastuzumab.

Based on available phase 3 trials, Vakaramoko Diaby, MSc, PhD, Florida A&M University (Tallahassee, FL), and colleagues constructed a Markov model to evaluate the cost effectiveness of first-line THP, followed by second-line T-DMI, and third-line lapatinib/capecitabine in patients with newly diagnosed HER2-positive metastatic breast cancer compared with other possible sequencing strategies. The model followed patients weekly over their remaining life expectancies. Health states considered were progression-free survival from first-line to third-line and death. Costs (2015 US dollars) were identified according to the Centers for Medicare & Medicaid Services drug payment and physician fee schedule. Outcomes measured included costs and quality-adjusted life years (QALYs).

Consistent with phase 3 clinical trials, THP as first-line therapy, T-DMI as second-line therapy, and lapatinib/capecitabine third-line therapy was the most clinically effective sequence but was associated with the highest total cost in the base-case analysis. This sequence resulted in 1.81 QALYs, at a cost of $335,231.35. For the treatment strategy to be a cost-effective approach, the willingness to pay threshold would have to be $398,444.17 per QALY. The combination of trastuzumab/docetaxel as first line without subsequent T-DMI or pertuzumab yielded 1.41 QALYs, at a cost of $175,240.69. For this sequence to be a cost-effective approach, the willingness to pay threshold would have to be $197,012.54. The least clinically effective sequence was trastuzumab/docetaxel as first-line therapy, T-DMI as second-line therapy, and trastuzumab/lapatinib as third-line therapy (1.27 QALYs), but it was the most cost effective at a total cost of $149,250.19.

If a value-based pricing approach was utilized, the study findings suggest that THP as first-line therapy, followed by T-DMI as second-line therapy, would require at least a 50% reduction in the total drug acquisition cost for this drug sequence to be considered a cost-effective strategy.

“The results of this study raise an important dilemma that has emerged in oncology, where the most clinically effective drugs are typically not the most cost-effective therapeutic options. Thus, practitioners caring for cancer patients, who inherently wish to provide the most clinically effective treatments, are often faced with a difficult predicament,” said the researchers.—Eileen Koutnik-Fotopoulos


Diaby V, Adulin G, Ali AA, et al. Cost-effectiveness analysis of 1st through 3rd line sequential targeted therapy in HER2-positive metastatic breast cancer in the United States. Breast Cancer Res Treat. 2016;160(10:187-196.