Is neratinib following trastuzumab in early-stage HER2-positive breast cancer cost-effective?

person Naomi RM Schwartz University of Washington, Seattle, WA info_outline Naomi RM Schwartz, Meghan Rose Flanagan, Joseph B Babigumira, Lotte Maria Gertruda Steuten, Joshua A. Roth

Authors person Naomi RM Schwartz University of Washington, Seattle, WA info_outline Naomi RM Schwartz, Meghan Rose Flanagan, Joseph B Babigumira, Lotte Maria Gertruda Steuten, Joshua A. Roth Organizations University of Washington, Seattle, WA, Memorial Sloan Kettering Cancer Center, New York, NY, Fred Hutchinson Cancer Research Center, Seattle, WA Abstract Disclosures Research Funding Other Background: Neratinib after adjuvant trastuzumab significantly improves disease-free survival (DFS) in human epidermal growth factor receptor 2-postiive (HER2+) breast cancer, but the median absolute DFS gain is only 1.3 months. There has been much controversy in the clinical and lay media as to whether the substantial cost of neratinib is justified by its effects, including a prominent ASCO Post article from Dr. Vogl about a year ago. We performed a cost-utility analysis to formally assess the value of adding neratinib based on Phase III ExteNET trial results. Methods: We developed a Markov state-transition model to assess the value of neratinib in Stage I-III HER2+ breast cancer. Five-year recurrence rates were derived from ExteNet. Mortality and recurrence rates after 5 years were derived from the HERceptin Adjuvant (HERA) trial. Costs were derived from wholesale acquisition costs and peer-reviewed literature. Health state utilities were derived from ExteNET and prior publications. Outcomes included life years (LY), quality-adjusted life years (QALYs), direct medical expenditures, and cost per QALY gained. The analysis took a payer perspective over a lifetime horizon and results were discounted at 3% per year. One-way and probabilistic analyses were conducted to evaluate uncertainty. As neratinib conferred more clinical benefit in hormone receptor-positive (HR+) disease, we also assessed value in that specific subgroup. Results: Base case results are presented in Table. At typical U.S. willingness to pay thresholds of $100,000 and $150,000 per QALY gained, neratinib had 16.7% and 27.2%, probabilities of cost-effectiveness, respectively. In the HR+ subgroup, neratinib had a cost of $275,311 per QALY gained (19.9% & 31.2% probability of cost-effectiveness at $100,000 & $150,000 per QALY). Conclusions: In the first independent assessment of the value of neratinib after adjuvant trastuzumab, neratinib is not projected to be cost-effective, even among patients who derived the most clinical benefit. Future analyses should reassess the cost-effectiveness of neratinib treatment as trial data mature. Base case results. Results Neratinib Observation Difference Cost $317,619 $152,812 $164,806 LYs 18.31 18.17 0.14 QALYs 15.67 15.28 0.40 Cost per LY -- -- $1,183,223 Cost per QALY -- -- $416,106