Abstract
BACKGROUND: A highly anticipated multicenter phase 3 HARMONi-A study (NCT05184712) showed that ivonescimab plus chemotherapy greatly enhanced progression-free survival (PFS) in individuals with non‑squamous non-small cell lung cancer (nsq-NSCLC) after treatment with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) with an acceptable safety profile. This investigation systematically analyzed the cost-effectiveness of treating advanced/metastatic nsq-NSCLC with EGFR mutations with a combination of ivonescimab and chemotherapy from the standpoint of the Chinese healthcare system. METHODS: A decision-embedded Markov model with three specific health states was established for predicting the economic and health outcomes associated with ivonescimab plus chemotherapy or chemotherapy alone over a 10-year time frame. The key health outcomes in the study included life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and incremental net health benefits (INHBs). Extensive sensitivity analyses were performed to assess the stability and uncertainty of the model with parameter adjustments. Additionally, cohort analyses for relevant subgroups were performed. RESULTS: The base-case overall cost (efficacy) of ivonescimab plus chemotherapy was $41,354 (0.90 QALYs), which was more than $35,166 and 0.13 QALYs of chemotherapy alone. This yielded an ICER of $277,594 per additional QALY with a corresponding INHB of -0.82 QALYs, which was significantly higher than the willingness-to-pay (WTP) threshold of $36,997/QALY in China. The sensitivity analyses indicated that the ivonescimab cost was the dominant driver for ICER, while the model results remained stable irrespective of variations in the model parameters within given ranges. CONCLUSIONS: The findings indicate that for Chinese patients with nsq-NSCLC with EGFR who did not respond to EGFR-TKI therapy, the ivonescimab-chemotherapy combination is not cost-effective in the absence of price adjustment or any current charitable aid program.