BACKGROUND: Neratinib, an oral, irreversible tyrosine kinase inhibitor of multiple human epidermal growth factor receptors (HERs), is indicated for the extended adjuvant treatment of adult patients with, HER2-positive early-stage breast cancer (eBC) to follow adjuvant trastuzumab-based therapy in the United States (US). However, greater efficacy has been seen in patients with hormone receptor-positive (HR+) breast cancer and who initiated neratinib within 1 year of completing trastuzumab
OBJECTIVE: This study explores the cost-effectiveness of neratinib versus placebo from a US third-party payer perspective in adult patients with HR+ HER2-overexpressed/amplified eBC and who are less than 1 year from the completion of prior adjuvant trastuzumab-based therapy.
METHODS: A Markov model was constructed to model costs and health outcomes of neratinib and placebo over a lifetime horizon. The model consisted of five health states representing the primary stages of disease in eBC—disease-free, local recurrence, remission, distant recurrence, and dead—and corresponds to the primary and secondary endpoints in the neratinib ExteNET trial. Overall survival was modeled based on a combination of post-distant recurrence survival and general population mortality, assuming all cancer-related mortality would occur through the distant recurrence health state. Statistical extrapolation of invasive disease-free survival and post-distant recurrence survival were derived from the ExteNET clinical trial data as well as the proportion of local and distant recurrence and number of adverse events. Non-breast cancer-related mortality was derived from US life tables. Costs per treatment arm were calculated based on drug acquisition, administration, and monitoring costs as well as treatment costs for adverse events and health state-related medical resource use. Quality-adjusted life-years (QALYs) were estimated per health state, and disutilities were applied per adverse event independent of treatment. Utility values for the invasive disease-free survival health state and diarrhoea were estimated using the EQ-5D-3L data collected in ExteNET. Additional health state utilities and adverse events disutilities were identified from the literature. Costs were adjusted to 2020 US dollars. One-way (OWSA) and probabilistic sensitivity analyses (PSA) and scenario analyses were performed to investigate the robustness of the results. Further, analyses were performed to investigate the cost-effectiveness for the subgroup of patients who did not achieve a pathologic complete response (pCR) after neoadjuvant therapy.
RESULTS: The results of the base case analysis showed that, compared with placebo, neratinib treatment generated an additional 0.88 incremental QALYs, 0.99 incremental life-years, and a resulting cost per QALY gained of $56,367. The results were robust across multiple scenario analyses with incremental cost-effectiveness ratios (ICERs) below $70,000. OWSA showed that the parameters that most influenced the results were variations in treatment-related costs, efficacy, and health state utility values. The PSA indicated that the probability of neratinib being cost-effective at a $100,000 per QALY threshold was above 75%. The analysis for the subgroup of patients who did not achieve a pCR after neoadjuvant therapy resulted in an improved ICER.
CONCLUSIONS: The current cost-effectiveness analysis shows that neratinib is a cost-effective therapy for treating adult patients with HR+ HER2-overexpressed/amplified eBC and who are less than 1 year from the completion of prior adjuvant trastuzumab-based therapy in the US and in patients who did not achieve a pCR after neoadjuvant treatment.
