Economic value, affordability, and scale-up of adjuvant immunotherapies in lung cancer treatment: From cost-effectiveness decision to budget impact analysis.

BACKGROUND Adjuvant immunotherapies have transformed lung cancer management by improving survival and patient-reported quality of life. However, their high acquisition costs and uncertainty around real-world economic value raise concerns regarding health system affordability and long-term sustainability. This study assessed the cost-effectiveness of adjuvant immunotherapies and evaluated their projected budget impact under plausible real-world adoption scenarios. METHODS We systematically reviewed published economic evaluations of adjuvant immunotherapies in lung cancer from 2010 to 2024. Eligible studies included cost-effectiveness and cost-utility analyses comparing immune checkpoint inhibitors with standard chemotherapy or best supportive care. Data on costs, quality-adjusted life years (QALYs), incremental cost-effectiveness ratios (ICERs), and willingness-to-pay (WTP) thresholds were extracted and narratively synthesised. For therapies judged cost-effective, we conducted a five-year (2025-2029) budget impact analysis using ISPOR-consistent methods, with costs standardised to 2024 US dollars. Three adoption scenarios were modelled: a base-case phased adoption (10%-50%), an accelerated uptake scenario (30%-50%), and a restricted uptake scenario (10%-30%), to examine the sensitivity of affordability to alternative implementation pathways. RESULTS Thirty-five economic evaluations of adjuvant immunotherapies for lung cancer were included (33 NSCLC and 2 SCLC studies). Frequently evaluated agents were pembrolizumab (n=11), nivolumab (n=8), atezolizumab (n=6), and durvalumab (n=5), alongside emerging agents including icotinib, sintilimab, sugemalimab and camrelizumab. Overall, adjuvant immunotherapies were associated with improved health outcomes compared with standard chemotherapy, with incremental gains of ~0.3-0.5 QALYs in several US/European models and gains of ≥1.0 QALY in selected biomarker-defined population or Chinese cohorts. However, per-patient costs were substantially higher, ranging from modest increases (~US$4,000 with icotinib) to totals >US$230,000-390,000 for PD-1/PD-L1 based regimens and >10-fold higher than standard care in some middle-income settings. ICERs ranged from highly favourable estimates (e.g. icotinib ~US$3,440/QALY; selected pembrolizumab, sintilimab, sugemalimab, squamous-specific nivolumab and CAD strategies within local WTP thresholds) to clearly non-cost-effective values (>US$300,000-600,000/QALY) for broad, unselected use, combination regimens, and several SCLC indications. Fo interventions judged cost-effective, five-year dudget impact estimates for cost-effective options indicated substantial 5-year incremental spending (from low millions up to >US$400 million), while a small subset of regimens were cost-saving or near budget-neutral, underscoring the need for targeted adoption and price negotiation in the adjuvant setting. Under the base-case phased uptake scenario, budget impact increased steadily over time, with high-cost regimens such as pembrolizumab- and durvalumab-based strategies generating the largest cumulative five-year expenditure. Accelerated uptake substantially intensified short-term fiscal pressure, with first-year spending approximately tripling and over half of total five-year costs incurred within the first three years for several therapies. In contrast, restricted uptake reduced cumulative five-year budget impact by approximately one-third to nearly one-half, depending on the agent. CONCLUSIONS Adjuvant immunotherapies for lung cancer deliver meaningful clinical benefits, but their economic value and affordability are highly context-specific. While several strategies are cost-effective at the individual patient level, health system affordability is strongly influenced by the pace and scale of adoption. Scenario-based budget impact analyses demonstrate that accelerated uptake can impose substantial short-term fiscal pressure, whereas phased or restricted implementation markedly improves affordability without altering cost-effectiveness conclusions. These findings underscore the importance of integrating cost-effectiveness evidence with explicit consideration of budget impact, adoption strategies, and managed entry mechanisms to support sustainable and equitable scale-up of adjuvant immunotherapies in routine clinical practice. PROSPERO REGISTRATION NUMBER CRD420251127115.