International cost-effectiveness analysis of nivolumab plus ipilimumab-based for metastatic non-small cell lung cancer with PD-L1 lower than 1%
Highlight box
Key findings
• First-line nivolumab plus ipilimumab was deemed cost-effective for metastatic non-small cell lung cancer (NSCLC) with programmed cell death ligand 1 (PD-L1) lower than 1% in China but did not meet cost-effectiveness in the USA.
What is known and what is new?
• The recently conducted pooled trials of CheckMate 227 and CheckMate 9LA demonstrated that dual immunotherapy is effective in NSCLC with PD-L1 lower than 1%. Although immunotherapy drugs are effective, their high cost limits their clinical use.
• First-line nivolumab plus ipilimumab represents a cost-effective option for metastatic NSCLC with PD-L1 lower than 1% in China, but not in the USA. In addition, nivolumab plus ipilimumab was more suitable for patients with brain metastases and squamous carcinoma.
What is the implication, and what should change now?
• The findings suggested that when selecting nivolumab plus ipilimumab for NSCLC with PD-L1 lower than 1%, it is important to consider not only the balance of efficacy and cost but also the search dual immune checkpoint inhibitors for the most cost-effective specific population. The choice of expensive cost treatment strategies enables the improvement of cost-effectiveness by changing the administration method or reducing the drug price. These results provide valuable insights that may inform clinical decision-making, healthcare policy development, and reimbursement strategies for immunotherapy in advanced NSCLC.
Introduction
Lung cancer is the deadliest cancer type and is linked to the highest cancer-related morbidity globally, with over 240,000 new diagnoses and approximately 180,000 deaths reported in 2022. China and the USA account for 40% and 7% of global lung cancer deaths, respectively (1,2). Non-small cell lung cancer (NSCLC) represents close to 80% of all patients, with over 60% of cases diagnosed at advanced stages, leading to a 5-year survival rate of only 4% (3). Immune checkpoint inhibitors (ICIs) have dramatically altered treatment of NSCLC, increasingly replacing platinum-based chemotherapies as the first-line approach for treating advanced disease in patients without targetable genetic alterations (4). Inhibitors of anti-programmed cell death-1 (anti-PD-1) or anti-programmed death-ligand 1 (anti-PD-L1), including pembrolizumab, atezolizumab and cemiplimab, are recommended as first-line treatment options, used alone or in combination with chemotherapy. It has been found to be beneficial for NSCLC with PD-L1 expression greater than or equal to 1% (4) However, when these regimens were applied to patients with tumor PD-L1 lower than 1%, suboptimal long-term outcomes have been reported in response to chemo-immunotherapy, underscoring the need for improved, chemotherapy-free treatment strategies for this subgroup (5-7).
Nivolumab and ipilimumab are fully human monoclonal antibodies that target PD-1 and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), respectively, with high specificity and affinity (8). Their combination enhances PD-L1 expression in tumors with initially low PD-L1 levels, inhibits regulatory T-cell activity, and amplifies antitumor immune activity (8,9). Long-term randomized controlled trials (RCTs) have demonstrated substantial survival benefits with dual immunotherapy. Data pooled from the CheckMate 227 (NCT02477826) and CheckMate 9LA (NCT03215706) trials revealed that a combination of nivolumab and ipilimumab, irrespective of chemotherapy use, markedly improved both overall survival (OS) [median OS, 17.4 versus 11.3 months; hazard ratio (HR), 0.64; 95% confidence interval (CI): 0.54–0.76] and progression-free survival (PFS) (median PFS, 5.4 versus 4.9 months; HR, 0.72; 95% CI: 0.60–0.87) compared with chemotherapy in NSCLC with PD-L1 lower than 1% (10). These results support the implementation of personalized treatment regimens tailored to this high-risk population.
Despite these clinical benefits, the high cost of dual immunotherapy limits its accessibility and economic evaluation is needed to determine its value. Cost-effectiveness assessments help guide policymakers, healthcare providers, and patients in making informed decisions about the adoption of new treatments. The present investigation was conceptualized to determine the cost-effectiveness of first-line nivolumab plus ipilimumab compared to chemotherapy for treating metastatic NSCLC with PD-L1 lower than 1% from healthcare payer perspectives in the USA and China. We present this article in accordance with the CHEERS reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-222/rc).
Methods
Patient characteristics and clinical data for this analysis were extracted from the pooled of CheckMate 227 and CheckMate 9LA trial (10). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.
Patients and treatments
The model included 637 patients with recurrent or stage IV NSCLC, confirmed by histology, and PD-L1 lower than 1%. Patients were allocated to two treatment groups: the nivolumab plus ipilimumab group in which patients were given nivolumab (3 mg/kg every 2 weeks in the CheckMate 227 trial or 360 mg every 3 weeks in the CheckMate 9LA trial) in combination with ipilimumab (1 mg/kg every 6 weeks), with or without chemotherapy [non-squamous NSCLC (25.75% of patients): pemetrexed (500 mg/m2) together with cisplatin (75 mg/m2) or carboplatin (area under the curve =6); squamous NSCLC (74.25% of patients): paclitaxel (200 mg/m2) plus carboplatin, administered for up to four cycles every 3 weeks]; and the chemotherapy group in which patients received up to four cycles of chemotherapy every 3 weeks (Table S1). In the RCT protocol for post-progression treatment, 43.48% (140/322) and 52.38% (165/315) of patients in the nivolumab plus ipilimumab group and the chemotherapy group, respectively, received subsequent systemic therapy (4,10,11). Any remaining patients received best supportive care (BSC), including end-of-life care for up to 1 year before death. To estimate the treatment regimen’s costs and outcomes, baseline characteristics were standardized: the typical patient was male, 65 years old, with a serum creatinine level of 1 mg/dL, a body weight of 70 kg (USA) or 65 kg (China), and a body surface area (BSA) of 1.79 m2 (USA) or 1.72 m2 (China) (Table 1) (10,12-14).
Table 1
| Variables | Baseline value [range] (ref.) | Distribution |
|---|---|---|
| Clinical parameters | ||
| Weibull survival model for OS | ||
| Nivolumab plus ipilimumab group | Scale =0.085859 | NA |
| Shape =0.724024 | ||
| Chemotherapy group | Scale =0.089687 | NA |
| Shape =0.849698 | ||
| Weibull survival model for PFS | ||
| Nivolumab plus ipilimumab group | Scale =0.274740 | NA |
| Shape =0.552840 | ||
| Chemotherapy group | Scale =0.110011 | NA |
| Shape =1.150043 | ||
| Rate of receiving second-line therapy | ||
| Nivolumab plus ipilimumab group | 0.435 [0.348–0.522] (10) | Beta |
| Chemotherapy group | 0.524 [0.419–0.623] (10) | Beta |
| Risk for AEs in nivolumab plus ipilimumab group | ||
| Increased lipase | 0.066 [0.053–0.079] (10) | Beta |
| Risk for AEs in chemotherapy group | ||
| Anemia | 0.140 [0.112–0.168] (10) | Beta |
| Neutropenia | 0.114 [0.091–0.137] (10) | Beta |
| Discount rate | ||
| USA | 0.030 [0–0.036] (12) | Uniform |
| China | 0.050 [0–0.060] (12) | Uniform |
| Body weight (kg) | ||
| USA | 70 [30–200] (12) | Uniform |
| China | 65 [30–200] (12) | Uniform |
| Body surface area (m2) | ||
| USA | 1.790 [1.432–2.148] (13) | Uniform |
| China | 1.720 [1.376–2.064] (14) | Uniform |
| Health parameters | ||
| Utility and disutility | ||
| Utility of PFS | 0.710 [0.568–0.852] (15,16) | Beta |
| Utility of PD | 0.670 [0.536–0.804] (15,16) | Beta |
| Disutility of grade 3 or higher AEs | 0.055 [0.044–0.066] (13,14,17) | Beta |
AEs, adverse events; NA, not applicable; OS, overall survival; PD, progressive disease; PFS, progression-free survival.
Model structure
A comprehensive Markov model, incorporating three states of health—PFS, progressive disease (PD), and death—alongside a decision tree, was constructed to evaluate costs and efficacies of the different first-line treatment strategies for NSCLC with PD-L1 lower than 1% (Figure S1). The model employed a cycle length of 6 weeks and was structured to project outcomes over a patient’s lifetime. To account for time preference, annual discount rates of 3% and 5% were applied to cost and effectiveness outcomes in the USA and China, respectively (12). The primary model outputs included total costs, life-years (LYs), quality-adjusted LYs (QALYs), incremental cost-effectiveness ratios (ICERs), and incremental net health benefit (INHB) from healthcare payer perspectives in the USA and China, using respective willingness-to-pay (WTP) thresholds of $100,000/QALY and $36,255/QALY, corresponding to three times the gross domestic product (GDP) per capita in each country (12). A subgroup analysis was conducted to assess cost-effectiveness variations across different patient populations. Markov model construction was performed with TreeAge Pro 2020 (TreeAge Software, MA, USA, https://www.treeage.com).
Transition probabilities for PFS and death under each treatment strategy were derived from Kaplan-Meier survival curves, with survival model parameters extracted using the GetData Graph Digitizer (v 2.26; http://www.getdata-graph-digitizer.com/index.php). Several parametric survival models were evaluated such as the Gompertz, Weibull, log-logistic, exponential, and log-normal distributions, were evaluated. Model selection was according to the Akaike’s and Bayesian Information Criteria (AIC and BIC). Given its flexibility and ability to accommodate increasing or decreasing hazard functions, the Weibull distribution was chosen to estimate patient transitions across health states, particularly for events occurring early in the follow-up period (Figure S2 and Table S2). The shape (γ) and scale (λ) parameters of the Weibull model were estimated using R (v 4.4.2, http://www.r-project.org) (Table 1) (13).
Utility and cost inputs
Utility values were employed to quantify quality of life (QoL), capturing the impact of disease progression on patient well-being. Utility values ranged from 0 (worst health) to 1 (perfectly healthy). PFS and PD states had mean utilities of 0.710 and 0.670, respectively, as derived from the CheckMate 227 trial (15,16). Disutilities associated with grade 3 or higher adverse events (AEs) affecting >5% of patients were incorporated to refine utility estimates (13,14,17).
Direct medical costs encompassed expenditures for drug acquisition, AE management, tumor imaging/surveillance, drug administration, and end-of-life care (Table 2). Cost estimates for the USA were sourced from the Centers for Medicare & Medicaid Services and previous reports (12,13,18,19), whereas Chinese cost data were obtained from local hospital and prior study (14). Adjustments of costs to 2024 levels were based on the US consumer price index (20), while Chinese costs remained unadjusted due to relative price stability. Chinese costs were converted to US dollars at 1 USD =7.25 CNY (January 2025).
Table 2
| Cost parameters ($) | USA ($) [baseline value (range) (ref.)] |
China ($) [baseline value (range) (ref.)] |
Distribution |
|---|---|---|---|
| Drug† | |||
| Nivolumab per mg | 32 [26–39] (18) | 3 [2–4] | Gamma |
| Ipilimumab per mg | 180 [144–216] (18) | 50 [40–60] | Gamma |
| Chemotherapy per cycle | 7,399 [5,919–8,879] (18) | 1,009 [807–1,211] | Gamma |
| Second-line per cycle† | |||
| Nivolumab plus ipilimumab | 2,561 [2,049–3,073] (18) | 747 [598–896] | Gamma |
| Chemotherapy | 9,535 [7,628–11,422] (18) | 1,264 [1,011–1,517] | Gamma |
| AEs | |||
| Chemotherapy | 5,792 [4,634–6,950] (19) | 120 [96–144] (14) | Gamma |
| Drug administration per cycle | 623 [498–748] (13) | 627 [502–752] (14) | Gamma |
| Imaging/surveillance per cycle | 161 [129–193] (13) | 34 [27–41] (14) | Gamma |
| Best supportive care per cycle | 5,540 [4,432–6,648] (19) | 206 [165–247] (14) | Gamma |
| End-of-life per patient | 14,536 [11,629–17,443] (12) | 2,070 [1,656–2,484] (14) | Gamma |
†, China drug price from local sources in 2025. AEs, adverse events.
Statistical analysis
A range of sensitivity analyses were employed for evaluating the robustness of the model. One-way analysis was utilized to assess the effects of varying individual parameters by ±20% from their baseline values, following standard methodologies for examining parameter influence on ICERs (13). Probabilistic analysis was performed with 10,000 Monte Carlo simulations to simultaneously explore variability in multiple parameters (14). Sensitivity analysis results were visualized using tornado diagrams, acceptability curves, and scatter plots.
Subgroup analyses were conducted on pooled trial populations, stratifying patients by age, sex, Eastern Cooperative Oncology Group (ECOG) performance status (PS), smoking history, tumor histological results, presence of liver metastases, brain metastases, bone metastases, and prior therapy history (10). Given that OS and PFS survival curves for each subgroup were unavailable, nivolumab plus ipilimumab survival curves were generated using subgroup-specific HRs, following the approach described by Ding et al. (13).
Results
Baseline results
The developed model predicted that patients undergoing nivolumab plus ipilimumab treatment would have life expectancies of 3.85 and 3.51 LYs in the USA and China, respectively. These figures corresponded to gains of 1.64 LYs (19.7 months) and 1.40 LYs (16.8 months) relative to chemotherapy alone. When QoL adjustments were considered, patients receiving nivolumab plus ipilimumab achieved 2.61 and 2.39 QALYs, representing additional gains of 1.11 and 0.96 QALYs over chemotherapy in the USA and China, respectively. The total costs associated with nivolumab plus ipilimumab were $262,974 in the USA and $43,217 in China, yielding ICERs of $104,126/QALY (−0.04 QALYs) and $29,143/QALY (0.19 QALYs), respectively (Table 3). These findings suggest the cost-effectiveness of nivolumab plus ipilimumab for first-line advanced NSCLC treatment in Chinese patients with PD-L1 lower than 1%.
Table 3
| Treatment | Total cost ($) | Overall LYs | ICER ($/LY) | Overall QALYs | ICER ($/QALY) | INHB (QALYs) |
|---|---|---|---|---|---|---|
| USA | ||||||
| Chemotherapy group | 146,772 | 2.21 | Reference | 1.50 | Reference | Reference |
| Nivolumab plus ipilimumab group | 262,974 | 3.85 | 71,088 | 2.61 | 104,126 | −0.04 |
| China | ||||||
| Chemotherapy group | 15,269 | 2.11 | Reference | 1.43 | Reference | Reference |
| Nivolumab plus ipilimumab group | 43,217 | 3.51 | 19,937 | 2.39 | 29,143 | 0.19 |
ICER, incremental cost-effectiveness ratio; INHB, incremental net health benefits; LYs, life-years; QALYs, quality-adjusted life-years.
Sensitivity and subgroup analyses
One-way sensitivity analysis (Figure 1) identified patient body weight as the most influential variable affecting ICER estimates, with ICERs ranging from $17,993/QALY at 30 kg to $229,383/QALY at 200 kg. Other significant factors included the utility value of the PD state and ipilimumab cost, whereas the costs of drug administration, chemotherapy, and the risk of elevated lipase levels had minimal impact.
Probabilistic sensitivity analysis results, depicted in the ICER scatter plot (Figure S3), indicated that the odds of cost-effectiveness for nivolumab plus ipilimumab compared to chemotherapy was 43.6% and 70.0% at WTP thresholds of $100,000/QALY and $36,522/QALY in the USA and China, respectively. The acceptability curve (Figure 2) revealed changes in cost-effectiveness with altered WTP thresholds and demonstrated that at WTP thresholds of approximately $95,000/QALY and $26,000/QALY, nivolumab plus ipilimumab reached a 50% chance of being cost-effective relative to chemotherapy alone.
Subgroup analyses indicated that the patients for whom nivolumab plus ipilimumab was most cost-effective were those individuals brain metastases [ICER: $87,787/QALY (USA) and $20,985/QALY (China); INHB: 0.24 QALYs and 0.71 QALYs; Cost-effectiveness probability: 64.0% and 79.0%]. This was followed by patients with squamous cell carcinoma [ICER: $90,749/QALY (USA) and $23,104/QALY (China); INHB: 0.14 QALY and 0.52 QALY; Cost-effectiveness probability: 62.3% and 77.9%] and those with prior platinum-based chemotherapy [ICER: $95,620/QALY (USA) and $24,178/QALY (China); INHB: 0.07 QALY and 0.46 QALY; Cost-effectiveness probability: 61.7% and 75.9%] (Table 4).
Table 4
| Subgroup | HR (95% CI) | USA | China | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| OS | PFS | ICER ($/QALY) | INHB (QALYs) | Cost-effectiveness probability of nivolumab plus ipilimumab (%) | ICER ($/QALY) | INHB (QALYs) | Cost-effectiveness probability of nivolumab plus ipilimumab (%) | |||
| Age (years) | ||||||||||
| <65 | 0.66 (0.52–0.83) | – | 128,379 | −0.23 | 31.0 | 37,668 | −0.02 | 52.4 | ||
| ≥65 and <75 | 0.62 (0.47–0.81) | – | 117838 | −0.17 | 38.7 | 33,300 | 0.08 | 62.2 | ||
| ≥75 and <85 | 0.73 (0.38–1.39) | – | 153,682 | −0.31 | 1.2 | 48,216 | −0.18 | 25.5 | ||
| Sex | ||||||||||
| Male | 0.59 (0.48–0.72) | – | 111,179 | −0.13 | 51.5 | 27,423 | 0.29 | 74.9 | ||
| Female | 0.77 (0.56–1.06) | – | 174,514 | −0.37 | 0 | 56,945 | −0.24 | 0 | ||
| ECOG PS | ||||||||||
| 0 | 0.60 (0.45–0.81) | – | 113,297 | −0.14 | 45.5 | 31,425 | 0.13 | 67.9 | ||
| 1 | 0.67 (0.54–0.82) | – | 131,381 | −0.24 | 26.0 | 38,915 | −0.05 | 49.1 | ||
| Smoking status | ||||||||||
| Current or former | 0.63 (0.53–0.76) | – | 120,276 | −0.19 | 35.7 | 34,308 | 0.05 | 60.7 | ||
| Never smoked | 0.77 (0.49–1.20) | – | 174,514 | −0.37 | 0 | 56,945 | −0.24 | 0 | ||
| Tumor type | ||||||||||
| Squamous | 0.51 (0.36–0.72) | 0.60 (0.42–0.85) | 90,749 | 0.14 | 62.3 | 23,104 | 0.52 | 77.9 | ||
| Non-squamous | 0.69 (0.57–0.84) | 0.77 (0.63–0.95) | 153,832 | −0.38 | 0 | 43,029 | −0.11 | 46.4 | ||
| Brain metastasis | ||||||||||
| Yes | 0.44 (0.26–0.75) | – | 87,787 | 0.24 | 64.0 | 20,985 | 0.71 | 79.0 | ||
| No | 0.66 (0.55–0.78) | – | 128,379 | −0.23 | 31.0 | 37,668 | −0.02 | 52.4 | ||
| Liver metastasis | ||||||||||
| Yes | 0.74 (0.51–1.08) | – | 158,326 | −0.33 | 0 | 50,160 | −0.19 | 17.9 | ||
| No | 0.61 (0.51–0.74) | – | 115,514 | −0.16 | 43.1 | 32,340 | 0.11 | 67.9 | ||
| Bone metastasis | ||||||||||
| Yes | 0.62 (0.42–0.92) | – | 117,838 | −0.17 | 38.7 | 33,300 | 0.08 | 60.9 | ||
| No | 0.64 (0.53–0.77) | – | 122,839 | −0.21 | 33.6 | 35,369 | 0.02 | 60.3 | ||
| Prior therapy | ||||||||||
| Platinum-based chemotherapy | 0.50 (0.25–0.99) | – | 95,620 | 0.07 | 61.7 | 24,178 | 0.46 | 75.9 | ||
| Other chemotherapy | 0.56 (0.28–1.10) | – | 105,353 | −0.07 | 54.5 | 28,155 | 0.25 | 71.4 | ||
CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; ICER, incremental cost-effectiveness ratio; INHB, incremental net health benefits; OS, overall survival; PFS, progression-free survival; QALY, quality-adjusted life-year.
Discussion
Lung cancer imposes a substantial economic burden, with costs estimated at $18 billion as of 2020 (21). The medical expenses associated with lung cancer treatment in both the USA and China remain extremely high (22). ICIs have recently transformed cancer treatment paradigms. However, the high costs and limited availability of medical resources pose financial challenges for both individuals and society. Economic evaluations provide a systematic and theoretically grounded approach to assessing healthcare costs and outcomes, facilitating informed decision-making in resource allocation and policy development. The pivotal CheckMate 227 and CheckMate 9LA RCTs have demonstrated the survival benefits of the nivolumab-ipilimumab combination as a first-line approach for treating advanced NSCLC (23,24). Subsequent cost-effectiveness analyses conducted by Yang et al., Shu et al., and Mo et al. found that this combination treatment was not cost-effective relative to chemotherapy in the USA, China, and Japan (19,25,26). However, these studies failed to specifically explore the cost-effectiveness when PD-L1 expression lower than 1%. Given that the prevalence of metastatic NSCLC with PD-L1 expression lower than 1% has increased by 48% in real-world study (5), and the urgent need for corresponding RCTs and economic evaluations, this study aimed to address this gap through a pioneering analysis of cost-effectiveness from the payer perspective in the USA and China based on the findings from the two analyzed trials.
The present analyses revealed that the ICERs for first-line nivolumab plus ipilimumab compared with chemotherapy in advanced NSCLC with PD-L1 higher than 1% were $104,126/QALY and $29,143/QALY, respectively, in the USA and China, relative to the corresponding WTP thresholds of $100,000/QALY and $36,522/QALY. These findings suggest that the nivolumab-ipilimumab combination may be a more viable treatment strategy in China due to local affordability and market-based pricing mechanisms. Drug costs vary across regions due to market dynamics and healthcare policies, necessitating economic evaluations that account for multiple healthcare settings to enhance the generalizability of cost-effectiveness findings. One-way sensitivity analysis identified patient body weight as the most influential factor affecting cost-effectiveness outcomes. Further examination indicated that nivolumab plus ipilimumab was cost-effective among those weighing less than 50 kg in the USA and less than 80 kg in China. This raises ethical concerns regarding the financial burden on overweight or obese patients, who may face higher costs for the same life-sustaining treatment. Further analysis revealed that if the dose of ipilimumab is changed to 0.8 mg/kg or the ICIs administration interval is 6 weeks, it might be more cost-effective according to the existing standards. This might be worth referring to in future clinical practice, but larger sample RCTs are still needed for verification. A potential solution would be to shift from per-unit pricing of ICIs to a per-patient or per-treatment-cycle pricing model. Additionally, drug pricing played a crucial role in cost-effectiveness; with respective 8% and 28% reductions in the cost of nivolumab or ipilimumab, the ICERs in the USA ($99,129/QALY and $99,171/QALY) became cost-effective. These findings underscore the importance of incorporating cost considerations into pricing strategies and policy decisions to improve the affordability of these treatments.
Subgroup analyses further indicated that the nivolumab-ipilimumab combination represented the best cost-effectiveness among those with brain metastases, with probabilities of cost-effectiveness (INHB) reaching 64.0% (0.24 QALYs) in the USA and 79.0% (0.71 QALYs) in China. Despite the growing clinical relevance, RCTs specifically targeting brain metastases remain scarce, and many clinical trials either exclude such patients or analyze them as a subgroup. Preclinical study suggest that the brain microenvironment exhibits intrinsic immunosuppressive properties, highlighting the potential for immunotherapy-based combination strategies to serve as breakthrough treatments in this patient population (27). Consistent with these findings, Powell et al. conducted a pooled Analysis demonstrating that immunochemotherapy significantly improved OS (HR, 0.48; 95% CI: 0.32–0.70) and PFS (HR, 0.44; 95% CI: 0.31–0.62) in NSCLC with baseline brain metastases (28). Similarly, Zhu et al. conducted a network meta-analysis with an assessment of cost-effectiveness, reporting that immunotherapy-based combination regimens conferred greater benefits in small cell lung cancer with brain metastasis compared to chemotherapy alone (29). Furthermore, this study found that nivolumab plus ipilimumab exhibited similar cost-effectiveness trends in squamous cell carcinoma patients in both the USA and China, with probabilities of cost-effectiveness (INHB) of 62.3% (0.14 QALYs) and 77.9% (0.52 QALYs), respectively. From a broader perspective, identifying patient subgroups that respond most favorably to nivolumab plus ipilimumab could facilitate more cost-effective treatment strategies. Clinicians and healthcare policymakers should prioritize stratifying patient populations based on key characteristics to optimize treatment allocation and enhance cost-effectiveness outcomes.
Despite its strengths, there are several limitations in this study. First, the present analysis relied on pooled CheckMate 227 and CheckMate 9LA trial data, meaning that any biases present in these trials may also have influenced these results. Second, the long-term efficacy of nivolumab plus ipilimumab was extrapolated from clinical trial data, introducing inherent uncertainty. Third, costs associated with grade 1/2 and immune-related AEs were not included, which may have led to an overestimation of the benefits of dual immunotherapy. Finally, nivolumab plus ipilimumab in the treatment of NSCLC may have certain medical preferential policies in China, which may differ from those used by alternative public and private insurers. The absence of publicly available data on commercial insurance reimbursement poses challenges for conducting comprehensive cost-effectiveness analyses.
Conclusions
These findings indicate that first-line nivolumab plus ipilimumab is a cost-effective treatment relative to chemotherapy for advanced NSCLC with tumor PD-L1 lower than 1%, whereas cost-effectiveness is absent in the USA given the respective WTP thresholds. Additionally, the results of subgroup analyses suggest that patients with brain metastases, squamous cell carcinoma, and past platinum-based chemotherapy exposure may derive the greatest cost-effectiveness benefits from nivolumab plus ipilimumab. These results provide valuable insights that may inform clinical decision-making, healthcare policy development, and reimbursement strategies for immunotherapy in advanced NSCLC.
Acknowledgments
None.
Footnote
Reporting Checklist: The authors have completed the CHEERS reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-222/rc
Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-222/prf
Funding: This work was partly supported by
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-222/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.
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