Dataset Information

Cost-Effectiveness of Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer.

ABSTRACT:

Purpose

The Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) study showed a 15.7-month survival benefit with the addition of pertuzumab to docetaxel and trastuzumab (THP) as first-line treatment for patients with human epidermal growth factor receptor 2 (HER2) -overexpressing metastatic breast cancer. We performed a cost-effectiveness analysis to assess the value of adding pertuzumab.

Patient and methods

We developed a decision-analytic Markov model to evaluate the cost effectiveness of docetaxel plus trastuzumab (TH) with or without pertuzumab in US patients with metastatic breast cancer. The model followed patients weekly over their remaining lifetimes. Health states included stable disease, progressing disease, hospice, and death. Transition probabilities were based on the CLEOPATRA study. Costs reflected the 2014 Medicare rates. Health state utilities were the same as those used in other recent cost-effectiveness studies of trastuzumab and pertuzumab. Outcomes included health benefits expressed as discounted quality-adjusted life-years (QALYs), costs in US dollars, and cost effectiveness expressed as an incremental cost-effectiveness ratio. One- and multiway deterministic and probabilistic sensitivity analyses explored the effects of specific assumptions.

Results

Modeled median survival was 39.4 months for TH and 56.9 months for THP. The addition of pertuzumab resulted in an additional 1.81 life-years gained, or 0.62 QALYs, at a cost of $472,668 per QALY gained. Deterministic sensitivity analysis showed that THP is unlikely to be cost effective even under the most favorable assumptions, and probabilistic sensitivity analysis predicted 0% chance of cost effectiveness at a willingness to pay of $100,000 per QALY gained.

Conclusion

THP in patients with metastatic HER2-positive breast cancer is unlikely to be cost effective in the United States.

SUBMITTER: Durkee BY

PROVIDER: S-EPMC5070553 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: The clinical evaluation of HER2CLIMB trial showed a 21. 9-month median overall survival with the triplet regimens of tucatinib, capecitabine, and trastuzumab (TXT) for patients with human epidermal growth factor receptor 2 (HER2) -overexpressing metastatic breast cancer. From the payer's perspective of the United States and China, a cost-effectiveness analysis was conducted to evaluate the costs and benefits of adding tucatinib in this study. Methods: We constructed a Markov model for the economic evaluation of adding tucatinib to trastuzumab plus capecitabine in patients with HER-2 positive metastatic breast cancer in the United States and China. The model was conducted with a 10-year time horizon, and the health status was divided into three states: progression-free survival, progressing disease, and death. The health utility scores were consistent with published literature with similar patient status. The transition probabilities were derived from the survival data of the HER2CLIMB study. The unit prices of medicines were obtained from the West China Hospital, Red Book, and published literature. Outcomes were measured in quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio, which robustness was evaluated by deterministic and probabilistic sensitivity analyses. Results: Compared with the two-drug regimen of trastuzumab plus capecitabine (TX), the addition of tucatinib increased 0.21 QALY, with an increasing cost of $146,995.05 and $19,022.97 in the United States and China, respectively. The incremental cost-effectiveness ratios (ICERs) for the TXT versus TX was $699,976.43 in the U.S. and $90,585.57 in China, both of which are higher than their respective threshold of willingness to play. Deterministic sensitivity analysis shows that the price of tucatinib is the parameter that has the most significant impact on ICERs, but it does not change the results of the model. Probability sensitivity analysis shows that the probability of cost-effective for TXT is 0 in the base case. Conclusion: In the United States and China, tucatinib combined with trastuzumab and capecitabine is not cost-effective for patients with HER-2 positive metastatic breast cancer.

Project description:The median survival of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) has more than doubled, since the discovery of HER2-targeted treatments: it rose from less than 2 years in 2001 (prior introduction of trastuzumab) to more than 4 years in 2017. The initial generation of HER2-targeted therapies included trastuzumab with taxanes in the first line, followed by the addition of lapatinib and by a switch to another cytotoxic agent after progression. Results of CLEOPATRA, EMILIA, and TH3RESA trials have changed this clinical practice. The current consensus includes horizontal dual blockade (trastuzumab + pertuzumab) with taxanes or vinorelbine in the first line, followed by trastuzumab-emtansine (T-DM1) in the second line, with addition of lapatinib in the later lines of treatment. However, the fast and simultaneous development of new drugs led to a relative shortage of clinical evidence to support this sequence. Triple-positive breast cancers (TPBC), which express both hormonal receptors and HER2, constitute nearly half of HER2-positive cases. For these tumors, the current consensus is to add endocrine therapy after completion of cytotoxic treatment. Again, this consensus is not fully evidence-based. In view of the recent progress in treatment of estrogen-receptor positive breast cancers, a series of trials is evaluating addition of CDK4/6 inhibitors, aromatase inhibitors or fulvestrant to HER2-targeted and cytotoxic chemotherapy in TPBC patients. Despite the remarkable progress in treatment of HER2-positive breast cancer, metastatic disease is still incurable in the majority of patients. A wide range of novel therapies are under development to prevent and overcome resistance to current HER2-targeted agents. This review discusses pivotal clinical trials that have shaped current clinical practices, the current consensus recommendations, and the new experimental treatments in metastatic HER2-positive breast cancer.

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