Lung cancer is one of the most common malignancies in China and continues to pose a substantial threat to public health. According to the most recent data from the National Cancer Center (NCC), the crude incidence and mortality rates of lung cancer in 2022 reached 75.13 and 51.94 per 100,000 population, respectively, both of which were highest among all cancers nationwide (1). Non-small cell lung cancer (NSCLC) accounts for the vast majority of all lung cancer cases, with non-squamous histology representing the predominant subtype (2). Studies indicate that more than half of lung cancer patients in China are already at an advanced stage at the time of diagnosis, thereby losing the opportunity to undergo curative surgery (2–5). With the rapid advances in immuno-oncology over the past few years, systemic treatment strategies for NSCLC have made remarkable progress. In addition to conventional platinum-based doublet chemotherapy, programmed cell death-1 (PD-1) inhibitors have quickly become a central component of standard care. Multiple international and Chinese guidelines now recommend PD-1 inhibitors combined with pemetrexed and a platinum agent as a first-line standard regimen for patients with advanced NSCLC, especially those with non-squamous histology (6–8).

Several domestically developed PD-1 inhibitors have demonstrated robust and consistent clinical benefits in randomized controlled trials (RCTs) conducted among Chinese patients. As one of the earliest PD-1 inhibitors approved for NSCLC in China, toripalimab combined with chemotherapy significantly prolonged progression-free survival (PFS; median, 9.7 months), while overall survival (OS) had not yet been reached at the time of the primary analysis (median OS: not reached), and grade ≥3 adverse events were reported in 78.6% of patients (9). Similarly, camrelizumab in combination with pemetrexed and platinum chemotherapy achieved a marked improvement in PFS (median PFS: 11.0 months) and significantly prolonged overall survival (median OS: 27.1 months), with grade ≥3 adverse events observed in 70.7% of patients (10). In another large China-based phase III trial, sintilimab combined with pemetrexed and platinum chemotherapy resulted in substantial gains in PFS (median PFS: 8.9 months), while median OS was not reached at the time of reporting (median OS: not reached), and grade ≥3 adverse events occurred in 61.7% of patients (11). Across these phase III trials, the PD-1–based chemo-immunotherapy regimens demonstrated generally comparable efficacy profiles, while differences in the incidence and spectrum of treatment-related adverse events were observed among the regimens. Taken together, these phase 3 trial findings indicate that the major domestically developed PD-1 inhibitors in China have all demonstrated clear therapeutic efficacy in multiple phase III RCTs involving patients with advanced non-squamous NSCLC.

However, as China rapidly transitions into an aging society, the economic burden of lung cancer on the healthcare system has grown substantially, with drug expenditures being one of the major contributors to overall lung cancer–related medical costs (12). Although several domestically developed PD-1 inhibitors have been approved in recent years—greatly expanding the range of first-line treatment options and offering patients more opportunities for clinical benefit—the relative cost-effectiveness of these PD-1–based chemo-immunotherapy regimens in the Chinese healthcare context remains uncertain. In light of increasing pressure on the Chinese national medical insurance system, there is an urgent need for pharmacoeconomic evaluations based on Chinese clinical trial evidence and real-world cost data to compare the cost-effectiveness of different first-line immunotherapy strategies. Such analyses are essential to inform clinical decision-making and guide healthcare policy development.

To address this critical evidence gap and to comprehensively evaluate the cost-effectiveness of the major domestically developed PD-1 inhibitors in first-line therapy, rigorous pharmacoeconomic analyses based on Chinese clinical and cost data are needed to support clinical decision-making and policy planning, particularly in light of differences in drug acquisition costs and real-world market uptake despite similar reimbursement status. Therefore, this study aims to compare the cost-effectiveness of three domestic PD-1 inhibitors (sintilimab, toripalimab and camrelizumab) as first-line treatments for patients with advanced non-squamous non–small cell lung cancer in China.

This study evaluated the cost-effectiveness of three domestically developed PD-1 inhibitors, sintilimab, toripalimab and camrelizumab, for first-line treatment of advanced non-squamous NSCLC from the perspective of the Chinese national medical insurance system payer. All three immunotherapy regimens are included on the Chinese National Reimbursement Drug List and are widely used in clinical practice, making an economic comparison highly relevant for both policy and clinical decision-making. Based on the Markov model analysis and using three times China’s 2024 per capita GDP as the WTP threshold, camrelizumab emerged as the most cost-effective option. In probabilistic sensitivity analysis, the mean QALYs (95% uncertainty interval) were 1.1 (0.9–1.2) for sintilimab and 1.1 (1.0–1.2) for toripalimab. The substantial overlap in QALY distributions, combined with consistently higher total costs associated with toripalimab, supports its classification as a strictly dominated strategy. As a result, toripalimab was strictly dominated and showed no cost-effectiveness advantage under the conditions of this study.

Most previous cost-effectiveness analyses have compared a single PD-1 inhibitor combined with pemetrexed and platinum chemotherapy against chemotherapy alone (16, 18–23), and few studies have directly compared multiple major PD-1 inhibitors. Given the increasing use of domestically developed PD-1 inhibitors in China, evaluating the cost-effectiveness of several mainstream regimens simultaneously has important clinical and policy relevance. This study addresses an existing evidence gap in the literature. Findings from previous studies evaluating the cost-effectiveness of camrelizumab have not been consistent (16, 24, 25). The differences between earlier studies and the present analysis can be explained by several factors. First, the prices of PD-1 inhibitors and overall treatment costs in China vary annually and regionally depending on national reimbursement negotiations, procurement mechanisms and the level of medical institutions. By using real procurement prices from a specialty hospital in China, this study ensured that cost inputs closely reflected actual clinical practice, providing greater relevance and applicability compared with studies that relied on literature-derived or international pricing data. Second, the incidence of grade 3 or higher adverse events reported in phase III trials varies across PD-1 regimens. In China, the cost of managing adverse events, especially after disease progression, can account for a substantial portion of medical expenditures. As a result, heterogeneity in adverse event profiles can meaningfully affect ICER outcomes. The one-way sensitivity analysis in this study confirmed this pattern. Finally, this study reconstructed individual patient data using the Guyot method (13), applied several parametric survival distributions for extrapolation, and selected the best-fitting model based on the Akaike information criterion and the Bayesian information criterion. This approach improved the accuracy of long-term survival projections. Some earlier studies relied on simplified interpretations of Kaplan–Meier curves or used a single distribution for extrapolation, which may underestimate or overestimate the long-term benefits of PD-1 therapy and thereby shift ICER values (26, 27). In the probabilistic sensitivity analysis, survival uncertainty had a relatively small effect on the ICER, indicating that the transition probability estimates in this study were stable and robust.

A closer comparison of the three PD-1 inhibitors evaluated in this study indicates that the observed differences in cost-effectiveness can be attributed to three major drivers: drug acquisition costs and total treatment expenditures, the incidence and management costs of adverse events and the post-progression survival trajectories associated with each regimen. These factors jointly influence total costs and QALYs, ultimately determining the relative ICERs. First, camrelizumab demonstrated better progression-free survival and overall survival outcomes in clinical trials, resulting in the highest QALY gain in the model. Longer survival implies a longer duration of immunotherapy and additional subsequent medical spending, which increases its overall cost. However, the substantial incremental health benefit it provided kept its ICER well below commonly used WTP thresholds in China, making it the most cost-effective strategy overall. Second, although the health benefit of sintilimab was slightly lower than that of camrelizumab, its total cost was substantially lower. This allowed sintilimab to remain competitive at lower or moderate WTP levels. This finding highlights the critical role of drug acquisition costs in determining the cost-effectiveness of immunotherapy and is consistent with the one-way sensitivity analysis, in which drug price was identified as a principal driver. In contrast, toripalimab was more costly than sintilimab yet did not generate additional QALYs in the model. As a result, it offered no advantage in either cost or effectiveness and was strictly dominated. Neither its adverse event profile nor its post-progression survival trajectory was sufficient to offset its higher expenses, leading to markedly inferior cost-effectiveness compared with the other two PD-1 inhibitors.

From a health policy perspective, the findings of this study have important implications for reimbursement decision-making within the Chinese national medical insurance system. Although sintilimab, toripalimab, and camrelizumab are all included in the National Reimbursement Drug List following price negotiations, differences in long-term value remain when both clinical benefits and economic consequences are considered. Our results suggest that camrelizumab-based chemo-immunotherapy provides the greatest health gains and the highest probability of cost-effectiveness under commonly accepted WTP thresholds in China. Such evidence may support value-based resource allocation and inform future reimbursement adjustments, pricing negotiations, and clinical guideline development amid increasing budgetary pressure from an aging population and the rising burden of lung cancer.

There are several limitations to this study. First, the clinical effectiveness inputs were primarily derived from large randomized controlled trials, which are conducted under idealized conditions and may not fully represent real-world variations in treatment adherence, dosing frequency, comorbidity burden or subsequent therapy choices (28). Second, the three PD-1 regimens included in this analysis were not compared directly within the same clinical trial but were obtained from separate phase III studies. Although all included trials were conducted in China and evaluated similar first-line chemo-immunotherapy regimens, and reconstructed individual patient data together with multiple parametric survival models were applied to enhance comparability, this indirect comparison approach may still be subject to residual bias arising from differences in trial design, patient characteristics, follow-up duration, and post-progression treatment strategies (29). Furthermore, while our Markov model addresses the potential for logical inconsistencies (e.g., crossing survival curves) inherent in partitioned survival models (PSMs), it shares with PSMs the structural uncertainty associated with the choice of parametric distributions for long-term survival extrapolation. Third, the costs of post-progression treatments and adverse event management were sourced from published literature or hospital-level pricing data, which may introduce some uncertainty. Despite these limitations, the probabilistic sensitivity analysis showed that the main findings remained consistent across a wide range of parameter variations, supporting the robustness of the model results.

This study compared the cost-effectiveness of three major domestically developed PD-1 inhibitors for first-line treatment of advanced non-squamous non–small cell lung cancer in China. The findings indicate that camrelizumab is the most cost-effective option in the current medical insurance reimbursement environment, while sintilimab remains an attractive alternative for scenarios with lower WTP thresholds, given its lower total cost. These results provide useful evidence to inform clinical treatment selection and support policy development within the Chinese healthcare system. Further real-world data are needed to validate the long-term economic value of PD-1 therapies in routine clinical practice in China.