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Abstract

Background:

The COMPASSION-15 clinical trial demonstrated that cadonilimab plus chemotherapy significantly improved clinical benefits in human epidermal growth factor receptor 2-negative (HER2−) advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.

Objectives:

This study investigated the cost-effectiveness of cadonilimab plus chemotherapy in the first-line treatment for HER2− advanced G/GEJ adenocarcinoma from the Chinese healthcare system perspective.

Design:

Economic evaluation.

Methods:

We compared three treatment regimens based on the COMPASSION-15 trial, including chemotherapy, cadonilimab plus chemotherapy, and programmed death ligand 1 (PD-L1) test-guided treatment. A partitioned survival model was constructed at 21-day cycle lengths over a 10-year time horizon to predict total costs, life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) under the willingness-to-pay (WTP) threshold of three times the gross domestic product per capita ($40,334.05). Model parameters were obtained from a public bid-winning database and published literature. Scenario, one-way, and probabilistic sensitivity analyses were used to test the robustness of the model.

Results:

In the base case, the costs of chemotherapy, PD-L1 test-guided treatment, and cadonilimab plus chemotherapy were $7,207.78, $15,776.35, and $22,294.58, with QALYs of 0.59, 0.71, and 0.79, respectively. The ICERs of PD-L1 test-guided treatment and cadonilimab plus chemotherapy were $68,751.00 and $76,120.27 per QALY. The ICERs of cadonilimab plus chemotherapy were $58,469.16 and $121,123.92 per QALY for PD-L1 combined positive score (CPS) ⩾ 5 and <5 HER2− advanced G/GEJ adenocarcinoma. The cost of cadonilimab and patient weight were the most influential model parameters. Cadonilimab plus chemotherapy had a 0.01% cost-effectiveness in China.

Conclusion:

Cadonilimab plus chemotherapy might be a cost-effective regimen when the unit cost of cadonilimab was $151.48 (58% discount) and $188.04 (72% discount) for overall and PD-L1 CPS ⩾ 5 advanced G/GEJ adenocarcinoma.

Plain language summary

Economic evaluation of cadonilimab plus chemotherapy

This study investigated the cost-effectiveness of cadonilimab plus chemotherapy in the first-line treatment for patients with HER2- advanced gastric or gastroesophageal junction adenocarcinoma based on the COMPASSION-15 clinical trial from the Chinese healthcare system perspective. The results indicated that PD-L1 test-guided treatment and cadonilimab plus chemotherapy were not cost-effective at current price and the willingness-to-pay (WTP) threshold of three times the gross domestic product (GDP) per capita ($40,334.05). Cadonilimab plus chemotherapy might be a cost-effective regimen when the unit cost of cadonilimab was $151.48 (58% discount) for advanced G/GEJ adenocarcinoma.

Keywords

cadonilimab chemotherapy cost-effectiveness gastric or gastroesophageal junction adenocarcinoma human epidermal growth factor receptor 2-negative

Introduction

Gastric cancer (GC) is the third cause of cancer-related death and the fifth common malignancy in China, with 358,700 new cases and 260,400 deaths in 2022.¹ Despite the decreasing trend in incidence and mortality, GC continues to exert a significant impact on the cancer burden in China, as the majority of patients are diagnosed at advanced stages.² Gastric adenocarcinoma is the predominant histological type of GC, most of which are human epidermal growth factor receptor 2-negative (HER2−).³ Anti-programmed cell death protein-1 (PD-1) plus chemotherapy remains the standard first-line treatment of HER2− locally advanced or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma by the Chinese Society of Clinical Oncology (CSCO).⁴ The survival benefit of PD-1 inhibitor plus chemotherapy was relatively favorable in patients with high programmed death ligand 1 (PD-L1) expression.⁵ Therefore, novel treatments are urgently needed.

Cadonilimab, a PD-1 and cytotoxic T-lymphocyte antigen-4 bispecific antibody, was used for the treatment of cervical cancer, G/GEJ adenocarcinoma, and esophageal squamous cell carcinoma.^6,7 In the COMPASSION-15 clinical trial, cadonilimab plus chemotherapy resulted in significant improvements in progression-free survival (hazard ratio (HR): 0.55, 95% confidence interval (CI): 0.44–0.65) and overall survival (OS) (HR: 0.66, 95% CI: 0.54–0.81) in the first-line treatment of advanced HER2− G/GEJ adenocarcinoma.⁸ In patients with PD-L1 combined positive score (CPS) ⩾ 5, cadonilimab plus chemotherapy provided longer median progression-free survival (PFS) (6.9 months; HR: 0.51, 95% CI: 0.37–0.70) and OS (15.3 months; HR: 0.58, 95% CI: 0.41–0.82) than overall advanced HER2− G/GEJ adenocarcinoma.⁸ Treatment-related grade 3 and above adverse events (AEs) occurred in 65.9% of the cadonilimab group and 53.6% of the chemotherapy group, and the most common AEs were thrombocytopenia, neutropenia, and anemia.⁸

Cadonilimab was first approved in China on June 29, 2022, and reimbursed under the basic medical insurance for the treatment of recurrent or metastatic cervical cancer.^7,9 In September 2024, the cadonilimab-related combination regimen was approved as a first-line treatment for unresectable, locally advanced, or metastatic G/GEJ adenocarcinoma, and recommended by the guidelines of CSCO Gastric Cancer 2025.⁴ However, it is not yet known whether the survival benefit of cadonilimab justifies the high cost. Therefore, this study aimed to evaluate the cost-effectiveness of cadonilimab plus chemotherapy in the first-line treatment for HER2− advanced G/GEJ adenocarcinoma from the Chinese healthcare system perspective. Our analysis provided the first economic evidence to support clinicians in making clinical decisions and decision-makers in allocating limited healthcare resources.

Methods

This economic evaluation was based on modeling techniques, price databases, and published literature, so ethics committee approval was exempted. Methodology adhered to the consolidated health economic evaluation reporting standards 2022 (CHEERS 2022)¹⁰ (Supplemental Table 1).

Patients and treatments

Eligible patients aged 18–75 years, with histopathologically confirmed unresectable, locally advanced, or metastatic HER2− G/GEJ adenocarcinoma.⁸ We compared three first-line treatment strategies. Strategy 1: cadonilimab plus chemotherapy. Strategy 2: chemotherapy. Strategy 3: all patients received PD-L1 test, and cadonilimab plus chemotherapy was used for PD-L1 CPS ⩾ 5 patients and chemotherapy for others. PD-L1 CPS ⩾ 5 and <5 patients were assigned according to 38% and 62%, respectively.⁸

Dosing regimens were based on the COMPASSION-15 trial: cadonilimab (10 mg/kg) administered intravenously in combination with six cycles chemotherapy (oxaliplatin 130 mg/m² intravenously on day 1 and capecitabine 1000 mg/m² orally twice daily on days 1–14) every 21-day cycle.⁸ All treatments were continued until disease progression, unacceptable toxicity, or withdrawal of consent.⁸ After disease progression, 60.98% and 92.79% of patients in cadonilimab and chemotherapy groups received subsequent treatment, respectively.⁸ Patients who received subsequent treatments were assigned to chemotherapy (paclitaxel), immunotherapy (tislelizumab and sintilimab), targeted therapy (apatinib), and best supportive care by 34.4%, 11.5%, 11.1%, and 3.9% in the cadonilimab group, and 47.9%, 22.3%, 20.3%, and 2.3% in the chemotherapy group, respectively.^4,8 Subsequent dosing strategies followed the guidelines of CSCO Gastric Cancer 2025.⁴

Model structure

We developed a partitioned survival model with three mutually exclusive health states (PFS, progressive disease, and death) to predict disease regression of advanced or metastatic HER2− G/GEJ adenocarcinoma over a 10-year time horizon from the perspective of the Chinese healthcare system (Figure 1). A 21-day cycle length was chosen for all treatment strategies, as cadonilimab and chemotherapy were administered every 3 weeks.⁸ Patients entered the model from the PFS state, and could either remain in the PFS state or progress to progressive disease or death states.¹¹ Once disease has progressed, the patient could only remain in the progressive disease state or transfer to death.¹¹ Primary model outcomes included the total costs, life years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) under the willingness-to-pay (WTP) threshold of three times the gross domestic product (GDP) per capita ($40,334.05).¹² All costs and QALYs were discounted annually at 5% with a range of 0%–8%, and half-cycle correction was applied.¹² The model was programmed in Microsoft Excel 2019. All costs were adjusted using the Consumer Price Index for healthcare and converted to US dollars with an exchange rate of 1$ = 7.1217 CNY.

Figure 1.

The structure of the partitioned survival model.

Clinical data

Kaplan–Meier curves for PFS and OS by treatment strategies were extracted to obtain estimates of individual patient data (IPD) using GetData Graph Digitizer 2.26. Then, we reconstructed the Kaplan–Meier curves with the IPD estimates based on the algorithm from Guyot et al.¹³ To extrapolate progression and death beyond the follow-up period, seven parametric survival models were employed to fit survival curves of various intervention arms in the COMPASSION-15 trial, including exponential, Weibull, gamma, generalized gamma, Gompertz, log-normal, and log-logistic models.¹⁴ Statistical analysis was carried out in R 4.3.2. We selected the optimal parametric survival model based on the Akaike information criterion, Bayesian information criterion, visual inspection, and clinical plausibility.¹⁵ In overall patients, Log-normal distributions were used to fit PFS curves, gamma and log-logistic distributions were used to fit OS curves in the chemotherapy and cadonilimab groups, respectively. In PD-L1 CPS ⩾ 5 patients, log-normal distributions were used to fit PFS and OS curves of cadonilimab groups, and in PD-L1 CPS < 5 patients, log-normal, and log-logistic distributions were used to fit PFS and OS curves of chemotherapy groups, respectively. In accordance with the International Society of Pharmacoeconomics and Outcomes Research-Society of Medical Decision Making (ISPOR-SMDM) Task Force Report on Model Transparency and Validation, face validity was assessed by two clinicians, and internal validity was assessed by extreme parameters and substantial code checking.¹⁶ The fitted results are shown in Supplemental Table 2 and Supplemental Figures 1–12.

Costs

Only direct medical expenditures were calculated in the model, including drugs, routine surveillance, management of severe AEs, subsequent treatment, and palliative care. The unit drug costs were derived from average bid-winning prices in 2024 from Yaozhi.com, one of the largest public drug bidding databases in China.¹⁷ Medication costs were calculated by the default patient weight of 65 kg with a subsequent body surface area of 1.72 m² in the base-case analysis.¹⁸ According to the guidelines of CSCO Gastric Cancer 2025, routine surveillance covered semiannual laboratory tests and computed tomography of the chest, abdomen and pelvis, as well as annual bone scan, and magnetic resonance imaging.⁴ The cost of routine surveillance was derived from the price list of medical services in public healthcare organizations. The management costs of AEs were calculated by multiplying costs associated with grade 3 or above AEs with an incidence of 5% or more by the incidence of individual adverse events, including thrombopenia, neutropenia, leukopenia, anemia, and hypokalemia.⁸ The costs of AEs and palliative care were gathered from previously published literature.^19–21

Health state utilities

Each health state was assigned a health utility value anchored in 0 (death) and 1 (perfect health), which was used to calculate QALYs.²² Health state utility values for PFS and PD states were 0.853 (95% CI: 0.819–0.887) and 0.610 (95% CI: 0.575–0.645), respectively.^23,24 The utility value for PFS state was extracted from a cross-sectional study enrolling 243 Chinese GC patients, which used the EuroQol 5-Dimensions 5-Level (EQ-5D-5L) scale and the Chinese value set to calculate utility values.²⁴ The utility value for progressive disease was obtained from the RAINBOW clinical trial, which used EQ-5D-3L to measure patient-reported outcomes of ramucirumab plus paclitaxel for previously treated G/GEJ adenocarcinoma.²³ The loss of QALYs due to severe AEs was estimated by multiplying the incidence of AEs by the corresponding disutility values.²⁵ Disutility values caused by severe AEs were collected from published studies.^26–29 The costs and utilities are presented in Table 1.

Table 1.

Model parameter.

Parameters	Baseline	Range		Distribution	Source
Parameters	Baseline	Minimum	Maximum	Distribution	Source
Costs ($)
Cadonilimab (125 mg)	261.17	208.94	313.41	Gamma	Yaozh
Oxaliplatin (50 mg)	23.99	19.19	28.79	Gamma	Yaozh
Capecitabine (500 mg)	1.77	1.41	2.12	Gamma	Yaozh
Apatinib (250 mg)	14.70	11.76	17.64	Gamma	Yaozh
Tislelizumab (100 mg)	176.02	140.81	211.22	Gamma	Yaozh
Sintilimab (100 mg)	151.65	121.32	181.98	Gamma	Yaozh
Paclitaxel (30 mg)	21.16	16.93	25.39	Gamma	Yaozh
Intravenous injection per time	5.62	4.49	6.74	Gamma	Local charge
Laboratory tests per time	70.21	56.17	84.25	Gamma	Local charge
CT (chest/abdomen/pelvis) per time	168.50	134.80	202.20	Gamma	Local charge
Bone scan per time	112.33	89.87	134.80	Gamma	Local charge
Magnetic resonance imaging per time	231.69	185.35	278.02	Gamma	Local charge
PD-L1 test	2106.24	1684.99	2527.49	Gamma	Local charge
Best supportive care	182.23	145.78	218.68	Gamma	21
Palliative care per time	1859.38	1487.50	2231.26	Gamma	19
Cost of decreased platelet count	1633.90	1307.12	1960.68	Gamma	20
Cost of decreased neutrophil count	608.52	486.82	730.22	Gamma	19
Cost of decreased white blood cell count	608.52	486.82	730.22	Gamma	19
Cost of anemia	482.30	385.84	578.76	Gamma	20
Cost of hypokalemia	3000.00	2400.00	3600.00	Gamma	21
Utility values
Utility of PFS	0.853	0.819	0.887	Beta	24
Utility of PD	0.610	0.575	0.645	Beta	23
Disutility values
Decreased platelet count	0.108	0.086	0.130	Beta	27
Decreased neutrophil count	0.200	0.160	0.240	Beta	29
Decreased white blood cell count	0.200	0.160	0.240	Beta	29
Anemia	0.070	0.056	0.084	Beta	26
Hypokalemia	0.120	0.096	0.144	Beta	28
Adverse events (%)
Decreased platelet count due to chemotherapy	25.00	20.00	30.00	Beta	8
Decreased neutrophil count due to chemotherapy	14.80	11.84	17.76	Beta	8
Decreased white blood cell count due to chemotherapy	6.25	5.00	7.50	Beta	8
Anemia of chemotherapy	12.50	10.00	15.00	Beta	8
Decreased platelet count due to cadonilimab	28.52	22.82	34.23	Beta	8
Decreased neutrophil count due to cadonilimab	15.08	12.07	18.10	Beta	8
Decreased white blood cell count due to cadonilimab	7.21	5.77	8.66	Beta	8
Anemia of cadonilimab	10.16	8.13	12.20	Beta	8
Hypokalemia of cadonilimab	5.90	4.72	7.08	Beta	8
Other parameters
Discount rate (%)	5.00	0.00	8.00	Beta	12
Body surface area (m²)	1.72	1.38	2.06	Normal	18
Patient weight (kg)	65.00	52.00	78.00	Normal	18

CT, computed tomography; PD, progressive disease; PFS, progression-free survival.

Subgroup and scenario analyses

In subgroup analyses, we explored the cost-effectiveness of cadonilimab plus chemotherapy versus chemotherapy in PD-L1 CPS ⩾ 5 and <5 patients based on the model structure and methodology used in the base-case analysis. In addition, we conducted four scenario analyses. First, price threshold analysis was employed to explore the most reasonable pricing for cadonilimab. Second, the utility value for PFS state was adjusted to 0.750, which was derived from the RAINBOW clinical trial and measured using the EQ-5D-3L and the UK population preferences.²³ Third, we used utility values from economic evaluations related to G/GEJ adenocarcinoma, with a utility value of 0.797 for PFS state and 0.577 for PD state.³⁰ Fourth, a shorter time horizon (5 years) was used to calculate ICER values with less extrapolation and efficacy assumptions.

Sensitivity analyses

One-way (OWSA) and probabilistic sensitivity analyses (PSA) were conducted to evaluate the robustness of the base-case results. In the OWSA, the estimated plausible range of the model parameters was based on either 95% CI in the published literature or assuming a 20% change from the base-case value.³¹ The results of OWSA were presented in the form of tornado diagrams. For the PSA, we specified probability distributions to the model parameters, and performed 10,000 second-order Monte Carlo simulations by simultaneously sampling the key parameters from prespecified distributions.³² Costs were characterized by Gamma distributions, and utilities, disutility values and incidence by Beta distributions.³³ The cost-effectiveness acceptability curves were generated to illustrate the most cost-effective treatment regimen under various WTP thresholds.

Results

Base-case results

Compared with chemotherapy, PD-L1 test-guided treatment and cadonilimab plus chemotherapy provided incremental QALYs of 0.12 and 0.20, and incremental LYs of 0.69 and 0.89 with incremental costs of $8568.56 and $15,086.80, respectively. The ICERs were $12,485.82 per LY and $68,751.00 per QALY for PD-L1 test-guided treatment, and $17,025.79 per LY and $76,120.27 per QALY for cadonilimab plus chemotherapy, respectively, in the first-line treatment of HER2− advanced G/GEJ adenocarcinoma from the Chinese healthcare system perspective. Compared with PD-L1 test-guided treatment, the ICERs of cadonilimab plus chemotherapy were $32,615.45 per LY and $88,605.08 per QALY (Table 2).

Table 2.

Base-case and subgroup results.

Strategy	Costs, $	LYs	QALYs	ICER ($/LY)		ICER ($/QALY)
Overall patients
Chemotherapy	7,207.78	1.11	0.59	—		—
PD-L1 test-guided treatment	15,776.35	1.80	0.71	12,485.82	—	68,751.00	—
Cadonilimab plus chemotherapy	22,294.58	2.00	0.79	17,025.79	32,615.45	76,120.27	88,605.08
PD-L1 CPS ⩾ 5 patients
Chemotherapy	7,088.66	1.06	0.57	—		—
Cadonilimab plus chemotherapy	23,467.21	2.48	0.85	11,579.02		58,469.16
PD-L1 CPS < 5 patients
Chemotherapy	7,657.07	1.38	0.63	—		—
Cadonilimab plus chemotherapy	23,202.56	1.85	0.76	32,738.22		121,123.92

CPS, combined positive score; ICER, incremental cost-effectiveness ratio; LY, life-year; PD-L1, programmed death ligand 1; QALY, quality-adjusted life-year.

Subgroup analyses

In comparison to the base-case results, cadonilimab plus chemotherapy provided higher LYs and QALYs with a lower ICER of $58,469.16 per QALY for PD-L1 CPS ⩾ 5 patients. However, cadonilimab plus chemotherapy provided lower LYs and QALYs with a higher ICER of $121,123.92 per QALY for PD-L1 CPS < 5 HER2− advanced G/GEJ adenocarcinoma (Table 2).

Scenario analyses

When the unit cost of cadonilimab was $151.48 (58% discount) and $125.36 (48% discount), cadonilimab plus chemotherapy and PD-L1 test-guided treatment would be the high-value options. When the unit cost of cadonilimab was $188.04 (72% discount) and $88.80 (34% discount), cadonilimab plus chemotherapy would be cost-effective for PD-L1 CPS ⩾ 5 and <5 HER2− advanced G/GEJ adenocarcinoma, respectively (Figure 2). Employing health utility values from other sources would increase ICERs, but neither cadonilimab plus chemotherapy nor PD-L1 test-guided treatment was cost-effective compared with chemotherapy (Supplemental Table 3). At the 5-year time horizon, the ICERs of PD-L1 test-guided treatment and cadonilimab plus chemotherapy versus chemotherapy were $70,895.58 per QALY and $78,019.48 per QALY, respectively (Supplemental Table 4).

Figure 2.

Scenario analysis results for price reductions of cadonilimab.

Sensitivity analyses

The most influential parameters were the cost of cadonilimab and patient weight. However, none of the parameters reduced ICERs below the WTP threshold. The ICERs ranged from $57,997.71 to $79,504.29 for PD-L1 test-guided treatment versus chemotherapy, and $59,271.35 to $92,969.18 for cadonilimab plus chemotherapy versus chemotherapy (Figure 3). The results of the OWSA confirmed that our model was robust. At the WTP threshold of $40,334.05, cadonilimab plus chemotherapy had 0.01% and 1.13% probabilities of being cost-effective compared with chemotherapy for overall and PD-L1 CPS ⩾ 5 HER2− advanced G/GEJ adenocarcinoma (Figure 4 and Supplemental Figures 13 and 14).

Figure 3.

Tornado diagram of the one-way sensitivity analysis results. (a) Cadonilimab plus chemotherapy versus chemotherapy, (b) PD-L1 test-guided treatment versus chemotherapy, and (c) cadonilimab plus chemotherapy versus PD-L1 test-guided treatment.

Figure 4.

The cost-effectiveness acceptability curve of the probabilistic sensitivity analysis results.

Discussion

Cadonilimab plus chemotherapy has been approved by the National Medical Products Administration for the treatment of cervical cancer and G/GEJ adenocarcinoma.^6–8 To our knowledge, this was the first cost-effectiveness analysis of cadonilimab plus chemotherapy as first-line treatment of HER2− advanced G/GEJ adenocarcinoma from the Chinese healthcare system perspective. This economic evaluation revealed that the ICERs of PD-L1 test-guided treatment and cadonilimab plus chemotherapy were $68,751.00 and $76,120.27 per QALY compared with chemotherapy, both exceeding the WTP threshold of $40,334.05 in China. Our findings provided critical insights for healthcare decision-makers and supported reimbursement decisions for medical insurance.

The unit cost of cadonilimab and patient weight were the most critical variables driving the results of the model. Although cadonilimab-based combination regimens significantly improved the survival benefits for HER2− advanced G/GEJ adenocarcinoma, the current pricing of cadonilimab dramatically exceeded its marginal clinical value. As a result, substantial price reductions would reverse its cost-effectiveness. Cost-effectiveness threshold analysis suggested that when the unit cost of cadonilimab was reduced to $151.48 and $125.36, the ICERs for cadonilimab plus chemotherapy and PD-L1 test-guided treatment were $39,895.11 per QALY and $40,254.78 per QALY lower than the WTP threshold of $40,334.05. Compared to overall and PD-L1 CPS < 5 HER2− advanced G/GEJ adenocarcinoma, cadonilimab plus chemotherapy had a higher probability of being cost-effective in PD-L1 CPS ⩾ 5 patients because lower price reductions were needed. In addition to the cost of cadonilimab, patient weight was another critical parameter because cadonilimab was administered based on body weight.^6–8 Thus, cadonilimab would be unfavorable in overweight or obese patients because of the higher dosages and expenditures required. Future clinical trials should investigate the suitable dosage and evaluate whether varying dosages influence the clinical efficacy and incidence of severe AEs associated with cadonilimab.

Apart from cadonilimab, nivolumab, pembrolizumab, sintilimab, and zolbetuximab were other available regimens for the first-line treatment of HER2− advanced G/GEJ adenocarcinoma.⁵ Three economic evaluations based on the CheckMate 649 clinical trial evaluated the cost-effectiveness of nivolumab plus chemotherapy versus chemotherapy as first-line treatment for advanced or metastatic HER2− G/GEJ adenocarcinoma using state-transitioned Markov models, and demonstrated that the ICER of nivolumab plus chemotherapy ranged from $191,266 per QALY to $430,185 per QALY, considerably higher than the WTP threshold of three times GDP per capita.^20,34,35 Nivolumab plus chemotherapy was unlikely to be a cost-effective first-line therapy in advanced HER2− G/GEJ adenocarcinoma from the Chinese healthcare system perspective.^20,34,35 Lang et al. developed a Markov model based on the KEYNOTE-859 clinical trial and revealed that pembrolizumab plus chemotherapy was cost-effective compared with chemotherapy in first-line treatment of PD-L1 CPS ⩾ 10 locally advanced or metastatic HER2− G/GEJ adenocarcinoma in China.³⁶ Two cost-effectiveness analyses established partitioned survival models to investigate the cost-effectiveness of sintilimab plus chemotherapy versus chemotherapy by the ORIENT-16 clinical trial and indicated that sintilimab plus chemotherapy was a cost-effective first-line treatment option for overall, PD-L1 CPS ⩾ 5 and <5 advanced HER2− G/GEJ adenocarcinoma in China.^37,38 Zolbetuximab, a chimeric IgG1 monoclonal antibody, significantly prolonged PFS (HR: 0.687, 95% CI: 0.544–0.866) and OS (HR: 0.771, 95% CI: 0.615–0.965) compared with chemotherapy in the first-line therapy for patients with CLDN18.2-positive, HER2− locally advanced unresectable or metastatic HER2− G/GEJ adenocarcinoma.³⁹ Three studies evaluated the cost-effectiveness of zolbetuximab plus CAPOX (capecitabine and oxaliplatin) based on the GLOW clinical trial and showed that the ICER of zolbetuximab plus CAPOX ranged from $185,353 per QALY to $388,186 per QALY in China.^19,40,41 In general, compared to imported drugs, domestically produced innovative drugs have become high-value therapeutic options by virtue of their relatively lower market prices.

Cervical and G/GEJ cancers were important indications for cadonilimab, and multi-center randomized controlled trials have been conducted in China.^6–8 In the COMPASSION-16 trial, cadonilimab plus chemotherapy significantly improved median PFS (12.7 months vs 8.1 months; HR: 0.62, 95% CI: 0.49–0.80) and median OS (27.0 months vs 22.8 months; HR: 0.64, 95% CI: 0.48–0.86) compared to chemotherapy as first-line treatment for recurrent or metastatic cervical cancer.⁶ Three cost-effectiveness analyses revealed that cadonilimab in combination with platinum-based chemotherapy with or without bevacizumab was not cost-effective as first-line treatment of persistent, recurrent, or metastatic cervical cancer from the Chinese healthcare system perspective.^42–44 The cost-effectiveness probability of cadonilimab would exceed 52% if the price of cadonilimab were reduced by 50%.⁴² Therefore, cadonilimab was more likely to be cost-effective in cervical cancer than HER2− advanced G/GEJ adenocarcinoma, as fewer price reductions were required.

Our model has several limitations. First, our long-term extrapolated data lacked external validation owing to the unavailability of real-world data (e.g., national cancer registries or observational cohorts) for comparison. In the scenario analyses, short-term results were consistent with long-term results, indicating that cadonilimab plus chemotherapy and PD-L1 test-guided treatment would not be cost-effective for treating HER2− advanced G/GEJ adenocarcinoma. Second, part of the cost data used in this study was derived from published literature and may differ from actual clinical costs, which might affect the base-case results. Third, health utility values were obtained from a Chinese cross-sectional study and a global randomized controlled trial, which might not fully align with the preferences of Chinese patients. Utility values represented important variables for model results, but alterations in each utility value did not substantially alter the results. The OWSA indicated that the lowest and highest ICERs associated with health utility values ranged from $72,940.02 per QALY to $79,590.48 per QALY for cadonilimab plus chemotherapy, and from $66,653.49 per QALY to $70,984.81 per QALY for PD-L1 test-guided treatment. Future studies may incorporate Chinese-specific preference data to further validate the findings. Fourth, only costs and disutility values associated with severe AEs (grade 3 and above with an incidence of ⩾5%) were considered in this model, which might lead to underestimation of costs and overestimation of health outcomes than those in clinical practice. Given the availability of data, future studies could incorporate the management costs and disutility values associated with all treatment-related AEs to obtain sufficiently accurate economic evidence. Finally, as second-line regimens were complex and individualized treatment choices, we assumed that paclitaxel, tislelizumab, sintilimab, apatinib, and best supportive care were the primary subsequent treatment options based on the COMPASSION-15 trial and the guidelines of CSCO Gastric Cancer 2025. This might differ somewhat from actual treatment options. Notwithstanding these limitations of our model, we have circumvented risk in terms of model construction and parameter acquisition, and believe that our conclusions are justified.

Conclusion

Cadonilimab plus chemotherapy and PD-L1 test-guided treatment might not be cost-effective compared with chemotherapy in the first-line treatment for HER2− advanced G/GEJ adenocarcinoma in China. When the unit cost of cadonilimab was $151.48 (58% discount), $188.04 (72% discount), and $88.80 (34% discount), cadonilimab plus chemotherapy was a cost-effective option for overall, PD-L1 CPS ⩾ 5 and <5 HER2− advanced G/GEJ adenocarcinoma, respectively.

Supplemental Material

sj-docx-1-tag-10.1177_17562848251366946 – Supplemental material for Cost-effectiveness of cadonilimab plus chemotherapy in the first-line treatment of HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma

Supplemental material, sj-docx-1-tag-10.1177_17562848251366946 for Cost-effectiveness of cadonilimab plus chemotherapy in the first-line treatment of HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma by Shixian Liu, Kaixuan Wang, Ruixue Wang, Hao Chen, Ziming Wan, Lei Dou and Shunping Li in Therapeutic Advances in Gastroenterology

Footnotes

Acknowledgements

None.

Declarations

ORCID iD

Shunping Li

Supplemental material

Supplemental material for this article is available online.

References

Han

Zheng

Zeng

, et al. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent 2024; 4: 47–53.

Liu

, et al. Health economic evaluation on population-based Helicobacter pylori eradication and endoscopic screening for gastric cancer prevention. Chin J Cancer Res 2023; 35: 595–605.

Van Cutsem

Bang

Y-J

Feng-Yi

, et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer 2015; 18: 476–484.

CSCO. Guidelines of Chinese Society of Clinical Oncology (CSCO) gastric cancer. Beijing: People’s Medical Publishing House (PMPH), 2025.

Beshr

Al Hayek

, et al. PD-1/PD-L1 inhibitors in combination with chemo or as monotherapy vs. Chemotherapy alone in advanced, unresectable HER2-negative gastric, gastroesophageal junction, and esophageal adenocarcinoma: a meta-analysis. Clin Oncol (R Coll Radiol) 2024; 36: 797–808.

Sun

Yang

, et al. Cadonilimab plus platinum-based chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer (COMPASSION-16): a randomised, double-blind, placebo-controlled phase 3 trial in China. Lancet 2024; 404: 1668–1676.

Keam

SJ.

Cadonilimab: first approval. Drugs 2022; 82: 1333–1339.

Shen

Zhang

, et al. First-line cadonilimab plus chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: a randomized, double-blind, phase 3 trial. Nat Med 2025; 31: 1163–1170.

Gao

, et al. Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial. Lancet Oncol 2023; 24: 1134–1146.

10.

Husereau

Drummond

Augustovski

, et al. Consolidated health economic evaluation reporting standards 2022 (CHEERS 2022) statement: updated reporting guidance for health economic evaluations. Value Health 2022; 25: 3–9.

11.

Smare

Lakhdari

Doan

, et al. Evaluating partitioned survival and Markov decision-analytic modeling approaches for use in cost-effectiveness analysis: estimating and comparing survival outcomes. PharmacoEconomics 2020; 38: 97–108.

12.

Liu

, et al. China guidelines for pharmacoeconomic evaluation 2020. Beijing: China Market Press, 2020.

13.

Guyot

Ades

Ouwens

, et al. Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves. BMC Med Res Methodol 2012; 12: 9.

14.

Ishak

Kreif

Benedict

, et al. Overview of parametric survival analysis for health-economic applications. PharmacoEconomics 2013; 31: 663–675.

15.

Latimer

NR.

Survival analysis for economic evaluations alongside clinical trials—extrapolation with patient-level data: inconsistencies, limitations, and a practical guide. Med Decis Making 2013; 33: 743–754.

16.

Eddy

Hollingworth

Caro

, et al. Model transparency and validation: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force–7. Value Health 2012; 15: 843–850.

17.

YaoZh. The big data service platform for China’s health industry: information query of drug BidWinning. Chongqing: YaoZh, 2024.

18.

Liu

Dou

Immune checkpoint inhibitors versus chemotherapy as second-line therapy for advanced oesophageal squamous cell carcinoma: a systematic review and economic evaluation. Therap Adv Gastroenterol 2024; 17: 17562848241233134.

19.

Lei

Zhang

You

, et al. First-line treatment with zolbetuximab plus CAPOX for ClDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: a cost-effectiveness analysis. Therap Adv Gastroenterol 2024; 17: 17562848241297052.

20.

Jiang

Wang

LXW

. Cost-effectiveness analysis of nivolumab plus standard chemotherapy versus chemotherapy alone for the first-line treatment of unresectable advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. Int J Clin Pharm 2022; 44: 499–506.

21.

Liu

Dou

Cost-effectiveness analysis of PD-1 inhibitors combined with chemotherapy as first-line therapy for advanced esophageal squamous-cell carcinoma in China. Front Pharmacol 2023; 14: 1055727.

22.

Kaplan

Hays

RD.

Health-related quality of life measurement in public health. Annu Rev Public Health 2022; 43: 355–373.

23.

Wilke

Muro

Van Cutsem

, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol 2014; 15: 1224–1235.

24.

Pan

C-W

J-Y

Zhu

Y-B

, et al. Comparison of EQ-5D-5L and EORTC QLU-C10D utilities in gastric cancer patients. Eur J Health Econ 2023; 24: 885–893.

25.

Chu

Choi

Ostvar

, et al. Cost-effectiveness of immune checkpoint inhibitors for microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer. Cancer 2019; 125: 278–289.

26.

Liu

Jiang

Dou

, et al. Cost-effectiveness analysis of serplulimab plus chemotherapy in the first-line treatment for PD-L1-positive esophageal squamous cell carcinoma in China. Front Immunol 2023; 14: 1172242.

27.

Tolley

Goad

, et al. Utility elicitation study in the UK general public for late-stage chronic lymphocytic leukaemia. Eur J Health Econ 2013; 14: 749–759.

28.

Dong

Lin

Zhong

, et al. Evaluation of tucatinib in HER2-positive breast cancer patients with brain metastases: a United States-based cost-effectiveness analysis. Clin Breast Cancer 2022; 22: e21–e29.

29.

Nafees

Lloyd

Dewilde

, et al. Health state utilities in non-small cell lung cancer: an international study. Asia Pac J Clin Oncol 2017; 13: e195–e203.

30.

Zhu

Liu

Zhu

, et al. Immune checkpoint inhibitors plus chemotherapy for HER2-negative advanced gastric/gastroesophageal junction cancer: a cost-effectiveness analysis. Therap Adv Gastroenterol 2023; 16: 17562848231207200.

31.

Jain

Grabner

Onukwugha

Sensitivity analysis in cost-effectiveness studies: from guidelines to practice. Pharmacoeconomics 2011; 29: 297–314.

32.

Doubilet

Begg

Weinstein

, et al. Probabilistic sensitivity analysis using Monte Carlo simulation: a practical approach. Med Decis Making 1985; 5: 157–177.

33.

Briggs

Weinstein

Fenwick

, et al. Model parameter estimation and uncertainty analysis: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force Working Group-6. Med Decis Making 2012; 32: 722–732.

34.

Shu

Ding

Zhang

Cost-effectiveness of nivolumab plus chemotherapy vs. Chemotherapy as first-line treatment for advanced gastric cancer/gastroesophageal junction cancer/esophagel adenocarcinoma in China. Front Oncol 2022; 12: 851522.

35.

Zhang

P-F

Shi

X-Q

Nivolumab plus chemotherapy versus chemotherapy alone as first-line treatment for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: a cost-effectiveness analysis. Cost Eff Resour Alloc 2023; 21: 65.

36.

Lang

Deng

, et al. Cost-effectiveness analysis of pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric/gastroesophageal junction cancer in the Chinese healthcare system. Expert Rev Pharmacoecon Outcomes Res 2024; 24: 1027–1042.

37.

Xiang

, et al. Cost-effectiveness analysis of first-line sintilimab plus chemotherapy vs. Chemotherapy alone for unresectable advanced or metastatic gastric or gastroesophageal junction cancer in China. Front Pharmacol 2024; 15: 1411571.

38.

Wan

Cost-utility of sintilimab plus chemotherapy vs chemotherapy as first-line treatment of advanced gastric or gastroesophageal junction cancer in China. Expert Rev Pharmacoecon Outcomes Res 2024; 24: 671–678.

39.

Shah

Shitara

Ajani

, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med 2023; 29: 2133–2141.

40.

Lai

Luo

Huang

, et al. The cost-effectiveness of zolbetuximab in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma. Pharmacogenomics 2024; 25: 249–257.

41.

Huang

You

, et al. Cost-effectiveness analysis of zolbetuximab plus mFOLFOX6 as the first-line treatment for CLDN18.2-positive, HER2-negative advanced gastric or gastroesophageal adenocarcinoma. Front Pharmacol 2023; 14: 1238009.

42.

Ding

Wang

Shu

, et al. Cost-effectiveness analysis of a first-line treatment with cadonilimab plus platinum-based chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer in China: COMPASSION-16 trial. J Pharm Policy Pract 2025; 18: 2464781.

43.

Xiang

Chen

, et al. Cadonilimab plus chemotherapy as first-line treatment for persistent, recurrent, or metastatic cervical cancer: a cost-effectiveness analysis. Front Immunol 2025; 16: 1562875.

44.

Wang

Liu

Wang

, et al. Cost-effectiveness analysis of cadonilimab plus bevacizumab and chemotherapy for persistent, recurrent, or metastatic cervical cancer. Front Immunol 2025; 16: 1594786.

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