Lung cancer is the most common type of cancer and a leading cause of cancer death worldwide (1, 2). In China, the incidence and mortality of lung cancer have ranked first (3). In 2015, the medical costs of treating lung cancer in China accounted for approximately 0.6% of total health costs (4), and approximately 85% of lung cancers are non-small-cell lung cancer (NSCLC), mostly at an advanced stage at the time of diagnosis, with a 5-year survival rate less than 18% (5–7). As early as 15 years ago, platinum-based adjuvant chemotherapy changed the standard treatment for completely resected early-stage NSCLC (stage IB-IIIA) (8– 9–11). In recent years, with the development of immune checkpoint inhibitors (ICIs), immunotherapy has been increasingly used in clinical practice, and the reactivation of T-cell antitumor function has been demonstrated by inhibiting the programmed cell death-1 (PD-1) and programmed cell death receptor ligand-1 (PD-L1) pathways (12–15). Due to the good clinical efficacy and safety of immunotherapy in preventing postoperative recurrence and metastasis, increasing the effect in combination with chemoradiotherapy, and maintaining treatment in lung cancer, the treatment mode for patients with early, non-metastatic NSCLC has been changed (16–23)

Atezolizumab is a humanized IgG1 monoclonal antibody that targets PD-L1, which binds to PD-L1 and allows PD-1 to bind to other ligands (PD-L2) – a process important in preventing severe adverse immunity events (such as pneumonia) are important (24). In 2020, the State Food and Drug Administration of China officially approved atezolizumab combined with chemotherapy as a first-line treatment for extensive-stage small cell lung cancer (25), and in 2022, it officially approved atezolizumab for the detection of adjuvant therapy in patients with stage II-IIIA NSCLC who are assessed to have ≥ 1% tumor cells (TC) positive PD-L1 staining, after surgical resection, and platinum-based chemotherapy. This is the first and only drug approved for post-operative adjuvant immunotherapy of NSCLC in China. However, there are few relevant studies on the efficacy and prognosis of atezolizumab in NSCLC in China. The prognosis analysis of patients with NSCLC treated with atezolizumab combined with chemotherapy found that the response rate of intervention was higher than that of the control group, and the difference had statistical significance (P< 0.05). There was no significant difference in the incidence rate of adverse reactions between the intervention group and the control group (P > 0.05). After treatment, the Karnofsky performance status (KPS) and quality of life (FACT-L) scores in the intervention group were higher than those in the control group, and the differences had statistical significance (P< 0.05). Atezolizumab combined with chemotherapy in the treatment of NSCLC has a significant effect, less adverse reactions, and can effectively improve the quality of life of patients (26). The IMpower010 Phase III study showed that treatment with atezolizumab improved disease-free survival compared with best supportive care (BSC) in stage II-IIIA patients with tumor cell expression (PD-L1) of 1% or more (HR 0.66; 95% CI 0.50-0.88; p = 0.0039) and improved PFS in all stage II-IIIA patients compared with BSC (0.79; 0.64–0.96; p = 0.020), with an HR for disease-free survival of 0.81 (0.67-0.99; p = 0.040) in the intention-to-treat (ITT) group. Fifty-three of 495 patients (11%) had grade 3 and 4 adverse events related to atezolizumab, and 4 patients (1%) had grade 5 adverse events (27).

Although atezolizumab has been shown to be effective in the patient group after adjuvant chemotherapy for stage IB-IIIA resectable NSCLC, the cost-effectiveness associated with this drug treatment has also received much attention, reflecting whether its high cost has potential value and effects in resource-limited China (28, 29). The aim of our analysis was to evaluate the cost-effectiveness of atezolizumab versus BSC as adjuvant therapy after platinum-based chemotherapy for stage IB-IIIA resectable NSCLC from the perspective of the Chinese health care system.

This study is the first to evaluate the cost-effectiveness of atezolizumab versus BSC as an adjuvant treatment strategy after postoperative platinum-based chemotherapy for early-stage NSCLC (PD-L1 TC ≥ 1% stage II – IIIA group, all stage II – IIIA groups, or the intention-to-treat group (stage IB – IIIA)) from the perspective of the Chinese health care system, Unlike studies using proportional hazards models (44, 45), parametric curves in this study were fitted to each treatment group separately (46, 47), and the reason for the crossover of the PFS curves may be due to the fact that atezolizumab showed a pretreatment advantage of different groups at different times. Our analysis showed that the use of atezolizumab as adjuvant therapy after platinum-based chemotherapy resulted in a higher ICER compared with the WTP threshold $(27,354/QALY) for the PD-L1 TC ≥ 1% stage II-IIIA group, all stage II-IIIA group, or the ITT group, making atezolizumab less likely to be cost-effective in patients after postoperative platinum-based chemotherapy for early NSCLC. The results of our one-way sensitivity analysis and PSA showed that this result has good stability.

Currently, atezolizumab is mainly used for the treatment of small cell lung cancer in China. No domestic and foreign scholars have found the health economic evaluation of atezolizumab versus BSC as adjuvant therapy after platinum-based chemotherapy for stage IB-IIIA resectable NSCLC. A recent study assessed the economic outcomes of atezolizumab versus platinum-based chemotherapy for first-line treatment of EGFR and ALK wild-type metastatic NSCLC in a group with high, high or intermediate PD-L1 expression and in any group with PD-L1 expression from a Chinese health authority perspective, based on the IMpower110 trial. The incremental cost of atezolizumab compared with chemotherapy was reported to be $112,744.35, and 0. 91QALYs, $81, 831.03,and 0. 57QALYs, $70,346.51, and 0. 42QALYs in groups with high, high, or intermediate PD-L1 expression, respectively, and in any group with PD-L1 expression. The results of univariate sensitivity analysis of the above studies were consistent with the results of this study, indicating that the cost of atezolizumab and the utility of PFS were the factors that had the greatest impact on the model results. It is worth noting that the ICERs of the above studies were much lower than those of the all-randomized stage II-IIIA group in this study and were similar to those of our PD-L1 TC ≥ 1% stage II-IIIA group, which could be due to the following causes. First, the control strategy in the study was different; the above study used chemotherapy, and this study used the BSC, and the risk of SAEs and management costs that occur with different drugs are quite different, so the estimated incremental costs of the two studies were also different. Second, the utility value of health status is different, and the PFS in the above study was 0.804, while the PFS in our model was 0.827. Third, the group and order of administration of atezolizumab in the study were different, and the clinical effects on patients were also different. In the above study, atezolizumab was used as a first-line drug for metastatic lung cancer with different PD-L1 expression statuses (high PD-L1 expression group, high or medium PD-L1 expression group and any PD-L1 expression group), producing 1.80 QALYs, 1.47 QALYs and 1.32 QALYs, respectively. In this study, atezolizumab was used as an adjuvant drug for the treatment of patients with early NSCLC after postoperative platinum-based chemotherapy (PD-L1 TC ≥ 1% II-IIIA group, all-stage II-IIIA group, ITT group), producing 3.81 QALYs. Therefore, we believe that the conclusions of the above studies are not comparable to those of our study.

In recent years, relying on pharmacoeconomic evidence, the Chinese government has reduced the prices of many anticancer drugs by 30-70% in price negotiations with pharmaceutical companies. The latest results of national health insurance negotiations in 2020 showed that the average price reduction of drugs with successful negotiations was 50.64%, so we explored the effect of price reduction on the model results. When PAP was not available, the price of atezolizumab was reduced to 50%, 55%, and 60% of the original price, the probability that atezolizumab being cost-effective was equal to or greater than 30% in the PD-L1 TC ≥ 1% II-IIIA group and less than or equal to 20% in all-stage II-IIIA group and ITT group. its price reduction was Markov models were constructed based on follow-up data from the IMpower010 trial and assessed separately in the PD-L1 TC ≥ 1% stage II – IIIA group, all stage II – IIIA groups, and the ITT group, cost-effectiveness of adjuvant atezolizumab to the acceptable probability of cost-effectiveness, with the most significant effect in the PD-L1 TC ≥ 1% stage II-IIIA group, but less effective in all stage II-IIIA groups or the ITT group. In patients with resectable NSCLC, the effect of the PAP strategy was the most significant in the stage II–IIIA subgroup whose tumors expressed PD-L1 TC≥1%. Therefore, to make atezolizumab cost-effective compared with BSC, this study recommends the implementation of the PAP strategy for the PD-L1 TC ≥ 1% stage II – IIIA group in patients after postoperative adjuvant chemotherapy for stage IB-IIIA resectable NSCLC; reducing the price of atezolizumab to less than 45% of the original price through price negotiations might make the drug cost-effective for patients with stage IB-IIIA resectable NSCLC. These findings have certain reference value for guiding policy makers in rationally allocating health resources.

Our study had several limitations. First, the KM survival curve was obtained from the IMpower010 trial to extrapolate the long-term clinical effect of the drug by fitting a parameter function, and the extrapolation time exceeded the real follow-up time of the trial, incurring inevitable limitations and perhaps lead to deviations between the model results and the actual situation. Second, some key clinical costs were derived from the literature rather than survey data from this study (34–40), such as the subsequent treatment cost of PD, considering only the cost of grade III/IV adverse events reported by ≥ 1% of patients in the IMpower010 trial, this may lead to inaccurate estimates of AE costs. By changing the model input within a certain range to run the probability sensitivity analysis, it was found that ICER was not sensitive to AE cost. Third, there was uncertainty in the long-term survival prediction of the IMpower010 trial, and the data must be continuously updated to validate our model results. Despite these limitations, we believe that this study accurately reflects the clinical treatment of resectable NSCLC in stage IB-IIIA in China.

From the perspective of the Chinese health care system, it is unlikely that the use of atezolizumab in the adjuvant treatment of Chinese patients with stage IB-IIIA resectable NSCLC after adjuvant chemotherapy (PD-L1 TC ≥ 1% stage II-IIIA group, all-stage randomized II-IIIA group, ITT group) is cost-effective. Implementing PAP or reducing drug prices might be the most effective measure to increase the cost-effectiveness of atezolizumab.

The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.

This cost-effectiveness analysis was based on a literature review and modeling techniques, the study did not require approval from an Institutional Research Ethics Board.

Conception and design, PC and QY. Analysis and interpretation, PC and QY. Data collection, PC and QY. Writing the article, PC. Critical revision of the article, PC, QY, JC, XJ, and YL. Final approval of the article, PC and QY. Overall responsibility, PC and QY. All authors contributed to the article and approved the submitted version.

This project was funded by the Key project of Department of Science and Technology of Sichuan Province (grant number 2020YFS0397).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.