Presentation (CTI)

OBJECTIVES: Metastatic non-squamous NSCLC is associated with rapid clinical deterioration, high symptom burden, and intensive, time-sensitive treatment pathways, which can generate substantial caregiving demands and broader family impacts. Omitting these spillover effects may therefore understate the full benefits of therapies that improve or preserve patients’ health-related quality of life (HRQoL). Therefore, we evaluated the cost-effectiveness of pembrolizumab plus platinum and pemetrexed chemotherapy versus relevant first-line comparators for metastatic, non-squamous NSCLC in the US, serving as a practical example for incorporating spillover effects in cost-effectiveness analysis.
METHODS: We developed a partitioned survival model of progression-free, progressed disease, and death health states. Clinical efficacy and safety inputs were derived from KEYNOTE-189, with overall survival (OS) and progression-free survival (PFS) extrapolated beyond trial follow-up using standard parametric methods. Costs (2025 USD) included drug acquisition/administration, adverse events, routine disease management, subsequent therapy, and end-of-life care. Health state utilities were derived from EQ-5D values. Spillover effects were incorporated using family member HRQoL decrements estimated in our prior study as a function of the patient’s HRQoL loss, generating combined QALYs (patient + family) over each model cycle and treatment arm. Costs and outcomes were discounted by 3% annually.
RESULTS: Pembrolizumab plus chemotherapy increased discounted patient QALYs by 1.658 versus chemotherapy alone, with incremental costs of $150,888 and an ICER of $104,823/QALY. When including spillover, incremental family QALYs were 1.98, yielding a combined ICER of $76,206/QALY. Results were most sensitive to patients’ utility values. These results suggested that at a willingness-to-pay threshold of $100,000/QALY, pembrolizumab plus chemotherapy was cost-effective after incorporating spillover effect.
CONCLUSIONS: By capturing family spillover effects, pembrolizumab plus chemotherapy appears more cost-effective for metastatic non-squamous NSCLC than conventional analyses suggest, reflecting additional QALYs gained through reductions in caregiver HRQoL losses. Omitting spillover effects may bias value assessments against interventions that meaningfully improve patient quality of life.