The effects of neoadjuvant sintilimab versus pembrolizumab combined with chemotherapy on resectable non-small cell lung cancer: a multicenter propensity score-matched study

Introduction

According to recent reports, lung cancer is the second most common cancer in men and women, accounting for 11% and 12% of cancer cases, respectively (1). Moreover, lung cancer has the highest mortality rate of all cancers, accounting for 21% of all cancer-related deaths (2). Immune checkpoint inhibitors (ICIs), such as pembrolizumab (Mercadon, NJ, USA) and sintilimab (Baekje Shenzhou Biotechnology Co., Ltd., Beijing, China), are marketed as anti-cancer drugs. Pembrolizumab is a humanized mouse monoclonal antibody, while sintilimab is a recombinant fully human IgG4 monoclonal antibody. Due to the variance in the drug structure, the two medications can exert different pharmacological effects (3).

In recent years, multiple phase III randomized controlled trials have further established the role of neoadjuvant/perioperative immunochemotherapy in resectable non-small cell lung cancer (NSCLC). The CheckMate 816 study was the first to demonstrate that neoadjuvant nivolumab combined with chemotherapy can significantly improve pathological complete response (pCR) and event-free survival (EFS) (4). Subsequently, perioperative studies such as KEYNOTE-671 (pembrolizumab), CheckMate 77T (nivolumab), and AEGEAN (durvalumab) reported positive results, showing significant EFS benefits and confirming the value of ICIs in the full perioperative treatment of resectable NSCLC patients (5-7).

The KEYNOTE-189, ORIENT-11, KEYNOTE-407, and ORIENT-12 trials showed the survival advantages of combining ICIs with chemotherapy over chemotherapy alone in the treatment of advanced NSCLC (8-12). Further phase-III clinical studies need to be conducted to validate these findings.

A novel treatment approach known as immunochemotherapy has been implemented in the treatment of lung cancer. The CheckMate 816 phase-III clinical study reported a pCR rate of 21% for neoadjuvant immunochemotherapy (13). Moreover, this same patient cohort showed a significant improvement in the 3-year overall survival (OS) rate compared to the control group. The findings of this first phase-III clinical trial provide robust evidence of the feasibility of combining chemotherapy with immunotherapy as neoadjuvant therapy (14). Sun et al. reported that the combination of sintilimab and chemotherapy as a neoadjuvant treatment for stage-IIIA/IIIB NSCLC resulted in impressive major pathological response (MPR) and pCR rates of 62.5% and 31.25%, respectively, among the 16 patients who underwent surgery (15). Other studies have reported similar results (16,17). Similarly, various studies have reported that NSCLC patients have achieved a pCR and MPR following neoadjuvant treatment using pembrolizumab in combination with chemotherapy (18-20).

To date, there has been no direct comparison of the specific efficacy of these two different ICIs (pembrolizumab and sintilimab) in the neoadjuvant therapy of resectable lung cancer. Therefore, using propensity score matching (PSM), this study aimed to evaluate the effectiveness of neoadjuvant immunochemotherapy in resectable NSCLC, and compare the effectiveness of the two ICIs (pembrolizumab and sintilimab) combined with chemotherapy in resectable NSCLC (21). We present this article in accordance with the STROBE reporting checklist (22) (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-aw-1256/rc).

Methods

This study is a retrospective study, and the data were obtained from the following two centers: Department of Thoracic Surgery, Tangdu Hospital of the Fourth Military Medical University and Department of Thoracic Surgery, The Third Affiliated Hospital of Chongqing Medical University

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This retrospective study was approved by the Ethics Committee of Tangdu Hospital of the Fourth Military Medical University (No. IIT202512-05-KYB-04-XWK). The Third Affiliated Hospital of Chongqing Medical University was informed and agreed with this study. Informed consent was taken from all the patients. This study was registered at the Research Registry (identifying number: researchregistry9146).

NSCLC patients who received neoadjuvant pembrolizumab or sintilimab in combination with chemotherapy and subsequently underwent surgery at the two hospitals between June 2018 and March 2024 were included in the analysis. The platinum agents used included cisplatin or carboplatin, based on physician preference and patient tolerance. Fewer than 3 cycles of neoadjuvant therapy were administered in cases of patient preference, logistical constraints, or early surgery scheduling, but not due to disease progression or severe toxicity. The general characteristics and clinical data of the patients were recorded, including sex, age, height, weight, body mass index (BMI), smoking history, chemotherapy, pathological type, cycles of neoadjuvant therapy, clinical stage, operation time, intraoperative blood loss, surgical method, extent of surgery, duration of chest tube usage (days), hospital stay (days), Response Evaluation Criteria in Solid Tumors (RECIST), and pathological evaluation results (i.e., pCR and MPR).

The adenocarcinoma patients received pemetrexed or paclitaxel (albumin-bound) in combination with platinum drugs. Meanwhile, the squamous cell carcinoma patients received paclitaxel (albumin-bound) or other drugs (gemcitabine, docetaxel, or paclitaxel) in combination with platinum drugs. The cycles of neoadjuvant therapy were categorized as <3 times, or ≥3 times. Clinical staging is determined based on contrast-enhanced computed tomography (CT) and/or positron emission tomography-computed tomography (PET-CT) performed before treatment. For cases suspected of mediastinal or supraclavicular lymph node metastasis, histological confirmation is obtained through endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) or endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Metastasis to the lymph nodes of the supraclavicular fossa was further confirmed by tissue biopsy. The surgical method (thoracotomy, conversion to thoracotomy, and robotic- or video-assisted thoracoscopic surgery) was recorded. The extent of surgery was classified as lobectomy, bilobectomy, bronchoplasty or sleeve resection, or pneumonectomy. Patients who are histologically confirmed to have NSCLC and are clinically staged as IB (tumor diameter ≥4 cm) to IIIB (T3N2) according to the 8th edition of the AJCC Cancer Staging Manual and are eligible for resection are included, while those with unresectable stage IIIC or IV disease are excluded.

A pCR was defined as the absence of tumor cells (including lymph nodes) after specimen resection; A MPR was defined as ≤10% residual tumor cells or the disappearance of primary tumor cells with lymph node metastasis. The RECIST 1.1 evaluation results, such as complete response, partial response, stable disease, and progressive disease, were defined using earlier techniques. A statistical analysis was conducted to estimate the objective response rates (ORRs) and non-ORRs.

Endpoint

The primary endpoint of the study was to evaluate the pCR of patients with resectable NSCLC after neoadjuvant ICI therapy (pembrolizumab or sintilimab) combined with chemotherapy. Additionally, the study aimed to compare the pCR rates of the two ICI groups using PSM. The secondary endpoints included the MPR rates, ORRs, and surgical safety, which were compared between the two ICI groups using a PSM analysis.

Follow-up

In the first two years after surgery, patients are followed up every 3–6 months, and thereafter every 6–12 months. Follow-up includes medical history, physical examination, chest CT, and/or abdominal ultrasound. As needed, brain MRI and bone scans are performed to assess suspected recurrence. OS is defined as the time from the date of surgery to death from any cause. EFS is defined as the time from the date of surgery to disease recurrence, progression, or death from any cause.

Statistical analysis

PSM was used to match the patients receiving the two ICIs. The propensity score was estimated using logistic regression models to predict the probability of the patients receiving each ICI based on confounding variables (i.e., sex, age, BMI, smoking, pathological type, neoadjuvant cycle, and clinical stage). Continuous variables (such as age and BMI) are presented as mean ± standard deviation or median (interquartile range) depending on their distribution. For ease of analysis, some continuous variables (such as age and BMI) are converted into binary variables based on clinical significance (e.g., age ≥60 vs. <60 years; BMI ≥24 vs. <24 kg/m²).

After PSM, an analysis was conducted using the “PSMATCH” function in SPSS 27. For the PSM, sex, age, BMI, smoking, pathological type, cycles of neoadjuvant therapy, and clinical stage were all considered matching factors for the analysis of the pCR in the pembrolizumab group (PG) and sintilimab group (SG) after neoadjuvant therapy. Based on the PSM, both patient groups underwent one-one nearest-neighbor matching, using a match caliper of 0.02 times the standard deviation. The median difference was subsequently estimated to evaluate the balance between the matched groups; an average difference of >0.05 indicated an imbalance.

The survival curves were estimated using the Kaplan-Meier method. All comparisons between the two groups were made using the log-rank test. If more than two groups were described in the survival analysis, the hazard ratio was calculated using the Cox proportional hazards model.

The non-parametric Mann-Whitney U test was employed to analyze the continuous variables that failed to follow a normal distribution after testing. The Chi-squared test was used for the categorical variables, and the results are presented as frequencies and proportions. Statistical significance was set at P<0.05. Univariate logistic regression analysis was used to explore the association between various clinicopathological factors (including sex, age, BMI, smoking history, pathological type, neoadjuvant treatment cycle, clinical stage, etc.) and pCR and ORR. The results are presented as odds ratios (ORs) with their 95% confidence intervals (CIs).

Results

Patient characteristics

Between June 1, 2018, and March 31, 2024, 366 patients were enrolled in the study: 163 in the SG, and 203 in the PG (Figure 1). There were no significant differences between the two groups in terms of sex, age, smoking, pathological type, clinical stage, and the time between surgery and final treatment. Patients with EGFR or ALK mutations were excluded from this study. The BMI values were unequally distributed across the SG and PG; the majority of the patients in the SG were in the normal weight range (68.1% vs. 55.2%, P=0.01). Further, in the SG, 113 patients (69.3%) underwent ≥3 cycles of neoadjuvant therapy, compared to 163 patients (80.3%) in the PG (P=0.02) (Table 1).

Figure 1 Study flowchart of patient enrollment. PSM, propensity score matching.

Efficacy evaluation

A total of 159 patients (43.4%) reached the primary endpoint of a pCR. Among them, 70 (42.9%) and 89 (43.8%) patients belonged to the SG and PG, respectively (P=0.86). Of the 366 patients, 235 achieved an MPR, and there were no significant differences between the SG and PG in terms of the MPR (108, 66.3% vs. 127, 62.6%; P=0.46). Additionally, no significant difference was observed between the PG and SG in ORR (116, 71.2% vs. 126, 62.1%; P=0.07) (Table 1).

Surgical outcomes

A total of 366 patients successfully underwent surgery. There were no significant differences between the SG and PG in terms of the median operative time, estimated blood loss, chest tube duration, postoperative hospital stays, surgical method, and extent of surgery (Table 2).

Prognostic effects of the pCR and ORR

A logistic regression analysis was conducted to identify the prognostic factors for the pCR or ORR. Notably, receiving <3 cycles of neoadjuvant therapy was considered a negative factor for achieving a pCR (P=0.01, 95% CI: 0.21–0.62), while squamous cell cancer was considered a promoting factor for achieving a pCR (P=0.005, 95% CI: 1.32–4.79) (Figure 2A). The predicted factors of the ORR were similar to those of the PCR. Squamous cell carcinoma was a positive predictor (P=0.02, 95% CI: 1.14–4.03) to PCR, while <3 cycles was a negative predictor (P=0.02, 95% CI: 0.33–0.92) to PCR (Figure 2B).

Figure 2 Logistic analysis of the pCR (A) and ORR (B) using the basic data. BMI, body mass index; ORR, objective response rate; pCR, pathological complete response.

Endpoint after PSM

After PSM, 140 matched pairs of patients from the SG and PG were identified. The pCR was exactly the right size between the SG and PG, respectively (63, 45.0% vs. 65, 45.0%, P>0.99) (Table 3). Further, no significant differences were observed between the two groups in terms of the MPR (98, 70% vs. 92, 65.7%, P=0.22) and ORR (93, 66.4% vs. 82, 58.6%, P=0.17) values (Table 1).

Surgical outcomes after PSM

After PSM, no significant differences were found between the two groups in terms of the median operative time, estimated blood loss, chest tube duration, postoperative hospital stays, surgical method, and extent of surgery (Table 2).

Survival analysis of OS

The OS of the patients was analyzed at the baseline and after PSM, none of the patients who were treated with neoadjuvant sintilimab or pembrolizumab combined with chemotherapy reached the median OS. The 1- and 3-year OS rates of the PG were 98.7% and 79.3%, respectively, while those of the SG were 98.1% and 75.6%, respectively (P=0.73) (Figure 3A). After PSM, the 1- and 3-year OS rates of the PG were 95.3% and 77.0%, respectively, while those of the SG were 98.8% and 79.4%, respectively (P=0.22). The PSM did not appear to have any effect on OS (Figure 3B).

Figure 3 OS of the SG and PG patients based on the baseline data (A) and PSM data (B). OS, overall survival; PG, pembrolizumab group; PSM, propensity score matching; SG, sintilimab group.

Squamous cell carcinoma subgroup analysis

A subgroup analysis of patients with squamous cell carcinoma was conducted. No significant differences were observed between the SG and PG in terms of sex, age, and clinical stage; however, significant differences were observed between the two groups in terms of the BMI, smoking, and cycles of neoadjuvant therapy. The BMI values were unequally distributed across the SG and PG; the majority of the patients in the SG were in the normal weight range (68.1% vs. 55.2%, P=0.01). Further, in the PG, 129 patients (79.6%) underwent ≥3 cycles of neoadjuvant therapy, compared to 89 patients (66.9%) in the SG (P=0.02). In the baseline and after PSM analyses, there were no significant differences between the two groups in terms of the pCR and ORR (Table 3).

Discussion

To our knowledge, this was the first supplementary study to examine real-world neoadjuvant immunotherapy data in a Chinese population. In this real-world setting, the combination of chemotherapy and immunotherapy as a preoperative treatment resulted in a pCR rate of 43.4%, which shows the effectiveness of the treatment for patients beyond the confines of clinical trials. Further, this study evaluated the therapeutic effects of different ICIs and chemotherapy combinations in actual clinical practice in China, and our findings provide valuable clinical guidance. Our initial results revealed no significant differences in the pCR and MPR rates between the two groups. Jiang et al. conducted a meta-analysis study that showed similar results, with MPR and pCR rates in the PG and SG of 46.8% (15.3–81.1%) and 37.5% (24.2–53.3%), respectively (23).

In this study, we confirmed that patients receiving ≥3 cycles of neoadjuvant therapy had higher pCR rates than those receiving <3 cycles. Wu et al. also observed that patients receiving either pembrolizumab or nivolumab in combination with chemotherapy had marginally lower pCR rates after 2 cycles than 3 cycles (34.2% vs. 42.3%) (24). The preliminary results of the prospective neoSCORE trial demonstrated a numerically higher MPR rate in the 3-cycle sintilimab combined with the chemotherapy group than the 2-cycle group (41.4% vs. 26.9%) (25). Therefore, in terms of the short-term efficacy of the neoadjuvant treatment, the pCR and MPR rates were higher when 3 cycles of neoadjuvant treatment were administered rather than 2 cycles (26). This finding may lead to more clinicians and patients accepting an extended neoadjuvant treatment period in clinical practice (27). However, further studies need to be conducted to confirm the specific effects.

Patients with a high BMI (≥24 kg/m²) were more likely to achieve a pCR. However, since its underlying mechanism still requires further research and lacks supporting data, we will not discuss it further. A history of smoking may be a predictive indicator of the pCR, and may be related to the prevalence of squamous cell carcinoma.

In this study, before PSM, the patients in the PG had a marginally higher pCR rate than those in the SG. The patients with squamous cell carcinoma constantly exhibited a marginally higher postoperative pCR rate than those with adenocarcinoma, regardless of PSM. The CheckMate 816 trial confirmed these findings (13). Additionally, the NCT02716038 trial reported different pCR trends between patients with adenocarcinoma and squamous cell carcinoma (33% vs. 50%) (28). The higher incidence of squamous cell carcinoma in the PG may explain this finding. Alternately, it may be that more patients in the SG were treated with ≤2 cycles. Unlike nivolumab and pembrolizumab, sintilimab targets the FG loop of PD-1, exhibiting a ~10 and 50 times stronger binding affinity, respectively. This heightened affinity may endow sintilimab with greater efficacy in blocking the PD-1/PD-L1 pathway, thus amplifying T cell antitumor activity. As a fully humanized monoclonal antibody, sintilimab also presents lower immunogenicity, potentially minimizing immune-related adverse events (29). Moreover, our study reported higher pCR rates (43.4%) compared to the KEYNOTE-671 trial (18.1%), which may be attributed to patient selection bias, as our cohort included only patients who completed neoadjuvant therapy and underwent resection. Additionally, differences in disease stage, pathological assessment criteria, and regional treatment patterns may contribute to this discrepancy.

Intraoperative patient safety is another area of concern. Liang et al. concluded that neoadjuvant immunotherapy combined with chemotherapy did not increase bleeding compared to chemotherapy alone (30). Similarly, we found that there was no significant difference between the two drugs in terms of the surgical process. Treatment-related adverse events of grade 3 or higher occurred in 18.4% of patients in the sintilimab group and 20.2% in the pembrolizumab group, with no significant difference between groups (P=0.65). The most common adverse events included neutropenia, fatigue, and rash.

Further, meta-analyses suggest that neoadjuvant immunotherapy has a low rate of delayed surgery, and does not increase surgical difficulties or perioperative risks. Some researchers have hypothesized that increased tissue fibrosis after neoadjuvant immunotherapy could make the operation more challenging; however, it remains unclear if tissue fibrosis is related to the prolongation of the treatment cycle (31).

This study had some limitations, including its sample size and retrospective design. Additionally, the pCR rate and ORR are only indicative of short-term efficacy; thus, long-term follow-up is required. And we regret that we were unable to test the PD-L1 levels in all patients. In addition, about 70% of the cases in this study were over 60 years old and were heavy smokers. OS may be influenced by different causes of death, such as myocardial ischemia, and so on. Since the data sources for this study are limited, the results may vary when extrapolated to the entire population. The potential impact of imbalance in the number of neoadjuvant therapy cycles among groups on the outcomes should not be overlooked either. Moreover, the data in this study rely on short-term outcome indicators (pCR, ORR, MPR) and lack mature survival data. Since our follow-up period was not long enough, for the sake of data rigor, we did not report the median survival. The primary limitation of this study lies in its retrospective design. Patients were assigned to SG or PG not randomly, but based on real-world clinical circumstances, such as drug availability at hospitals during different periods, insurance reimbursement policies, physician decisions, and patients' personal choices. Although we used PSM to balance known confounding factors, we cannot completely exclude bias from unmeasured confounders. Finally, although PSM efforts have reduced bias, the conclusions of this study still need to be ultimately validated through specifically designed phase III randomized controlled trials (especially non-inferiority trials) to confirm the equivalence of sintilimab and pembrolizumab in perioperative treatment. Retrospective studies have inherent limitations, and further exploration through prospective studies is warranted.

Conclusions

This study aimed to analyze the preliminary results of using neoadjuvant chemotherapy in combination with sintilimab or pembrolizumab in the treatment of resectable NSCLC through PSM. The logistic regression analysis showed that the squamous cell carcinoma and cycles of neoadjuvant treatment affected the pCR rates. Therefore, the above information was included in the PSM. After PSM, no significant differences were observed between the two groups in terms of the pCR rate, surgical blood loss, or operation time. Thus, the two ICIs may have a similar effect on resectable NSCLC. However, further research needs to be conducted to validate the specific survival data.

Acknowledgments

We would like to thank Dr. Wenwen Wang (Department of Statistics, Air Force Medical University) for his guidance and advice on the statistical methods employed in this study.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-aw-1256/rc

Data Sharing Statement: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-aw-1256/dss

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-aw-1256/prf

Funding: The present study was supported by grants from the National Natural Science Foundation of China (No. 82173252), and the Miaozi Talent Fund of Tangdu Hospital of Air Force Military Medical University.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-aw-1256/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. This retrospective study was approved by the Ethics Committee of Tangdu Hospital of the Fourth Military Medical University (No. IIT202512-05-KYB-04-XWK). The Third Affiliated Hospital of Chongqing Medical University was informed and agreed with this study. Informed consent was taken from all the patients.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Filho AM, Laversanne M, Ferlay J, et al. The GLOBOCAN 2022 cancer estimates: Data sources, methods, and a snapshot of the cancer burden worldwide. Int J Cancer 2025;156:1336-46. [Crossref] [PubMed]
2. Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022. CA Cancer J Clin 2022;72:7-33. [Crossref] [PubMed]
3. Houda I, Dickhoff C, Uyl-de Groot CA, et al. New systemic treatment paradigms in resectable non-small cell lung cancer and variations in patient access across Europe. Lancet Reg Health Eur 2024;38:100840. [Crossref] [PubMed]
4. Mitsudomi T, Ito H, Okada M, et al. Neoadjuvant nivolumab plus chemotherapy in resectable non-small-cell lung cancer in Japanese patients from CheckMate 816. Cancer Sci 2024;115:540-54. [Crossref] [PubMed]
5. Spicer JD, Garassino MC, Wakelee H, et al. Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab compared with neoadjuvant chemotherapy alone in patients with early-stage non-small-cell lung cancer (KEYNOTE-671): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2024;404:1240-52. [Crossref] [PubMed]
6. Brazel D, Nagasaka M. Checkmate 77T: Perioperative chemoimmunotherapy outperforms in early-stage NSCLC. Med 2024;5:852-5. [Crossref] [PubMed]
7. Clemente F, Unterländer M, Dolgova O, et al. The genomic history of the Aegean palatial civilizations. Cell 2021;184:2565-2586.e21. [Crossref] [PubMed]
8. Garassino MC, Gadgeel S, Esteban E, et al. Patient-reported outcomes following pembrolizumab or placebo plus pemetrexed and platinum in patients with previously untreated, metastatic, non-squamous non-small-cell lung cancer (KEYNOTE-189): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol 2020;21:387-97. [Crossref] [PubMed]
9. Yang Y, Wang Z, Fang J, et al. Efficacy and Safety of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC: a Randomized, Double-Blind, Phase 3 Study (Oncology pRogram by InnovENT anti-PD-1-11). J Thorac Oncol 2020;15:1636-46. [Crossref] [PubMed]
10. Zhou C, Wu L, Fan Y, et al. Sintilimab Plus Platinum and Gemcitabine as First-Line Treatment for Advanced or Metastatic Squamous NSCLC: Results From a Randomized, Double-Blind, Phase 3 Trial (ORIENT-12). J Thorac Oncol 2021;16:1501-11. [Crossref] [PubMed]
11. Paz-Ares L, Vicente D, Tafreshi A, et al. A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407. J Thorac Oncol 2020;15:1657-69. [Crossref] [PubMed]
12. Liu SY, Zhou Q, Yan HH, et al. Sintilimab Versus pembrolizumab in monotherapy or combination with chemotherapy as first-line therapy for advanced Non-Small-Cell Lung Cancer- results from phase 2 randomized clinical trial (CTONG1901). J Clin Oncol 2022;40:9032.
13. Forde PM, Spicer J, Lu S, et al. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med 2022;386:1973-85. [Crossref] [PubMed]
14. Liu SY, Feng WN, Wu YL. Immunotherapy in resectable NSCLC: Answering the question or questioning the answer? Cancer Cell 2024;42:727-31. [Crossref] [PubMed]
15. Zhang P, Dai J, Sun F, et al. Neoadjuvant Sintilimab and Chemotherapy for Resectable Stage IIIA Non-Small Cell Lung Cancer. Ann Thorac Surg 2022;114:949-58. [Crossref] [PubMed]
16. Lee JM, Brunelli A, Cummings AL, et al. Phase 3 Trials of Neoadjuvant, Perioperative, and Adjuvant Chemoimmunotherapy for Resectable, Early-Stage NSCLC: Comprehensive Review and Detailed Analysis. JTO Clin Res Rep 2025;6:100866. [Crossref] [PubMed]
17. Sorin M, Prosty C, Ghaleb L, et al. Neoadjuvant Chemoimmunotherapy for NSCLC: A Systematic Review and Meta-Analysis. JAMA Oncol 2024;10:621-33. [Crossref] [PubMed]
18. Feng Y, Sun W, Zhang J, et al. Neoadjuvant PD-1 inhibitor combines with chemotherapy versus neoadjuvant chemotherapy in resectable squamous cell carcinoma of the lung. Thorac Cancer 2022;13:442-52. [Crossref] [PubMed]
19. Eichhorn F, Klotz LV, Kriegsmann M, et al. Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Lung Cancer 2021;153:150-7. [Crossref] [PubMed]
20. Eichhorn F, Klotz LV, Bischoff H, et al. Neoadjuvant anti-programmed Death-1 immunotherapy by Pembrolizumab in resectable nodal positive stage II/IIIa non-small-cell lung cancer (NSCLC): the NEOMUN trial. BMC Cancer 2019;19:413. [Crossref] [PubMed]
21. Yan X, Duan H. 122P Comparison of the efficacy of neoadjuvant pembrolizumab vs sintilimab combination with chemotherapy in resectable lung cancer: A multicenter propensity score matching study. J Thorac Oncol 2023;18:S109-10.
22. Cuschieri S. The STROBE guidelines. Saudi J Anaesth 2019;13:S31-4. [Crossref] [PubMed]
23. Mountzios G, Remon J, Hendriks LEL, et al. Immune-checkpoint inhibition for resectable non-small-cell lung cancer - opportunities and challenges. Nat Rev Clin Oncol 2023;20:664-77. [Crossref] [PubMed]
24. Wu J, Hou L, E H, et al. Real-world clinical outcomes of neoadjuvant immunotherapy combined with chemotherapy in resectable non-small cell lung cancer. Lung Cancer 2022;165:115-23. [Crossref] [PubMed]
25. Shao M, Yao J, Wang Y, et al. Two vs three cycles of neoadjuvant sintilimab plus chemotherapy for resectable non-small-cell lung cancer: neoSCORE trial. Signal Transduct Target Ther 2023;8:146. [Crossref] [PubMed]
26. Barcellini L, Nardin S, Sacco G, et al. Immune Checkpoint Inhibitors and Targeted Therapies in Early-Stage Non-Small-Cell Lung Cancer: State-of-the-Art and Future Perspectives. Cancers (Basel) 2025;17:652. [Crossref] [PubMed]
27. Banna GL, Hassan MA, Signori A, et al. Neoadjuvant Chemo-Immunotherapy for Early-Stage Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis. JAMA Netw Open 2024;7:e246837. [Crossref] [PubMed]
28. Shu CA, Gainor JF, Awad MM, et al. Neoadjuvant atezolizumab and chemotherapy in patients with resectable non-small-cell lung cancer: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol 2020;21:786-95. [Crossref] [PubMed]
29. Chen S, Li T, Yang W, et al. Comparative efficacy of six programmed cell death Protein-1 inhibitors as first-line treatment for advanced non-small cell lung cancer: a multicenter retrospective cohort study. Front Pharmacol 2024;15:1390872. [Crossref] [PubMed]
30. Liang H, Yang C, Gonzalez-Rivas D, et al. Sleeve lobectomy after neoadjuvant chemoimmunotherapy/chemotherapy for local advanced non-small cell lung cancer. Transl Lung Cancer Res 2021;10:143-55. [Crossref] [PubMed]
31. Cottrell TR, Thompson ED, Forde PM, et al. Pathologic features of response to neoadjuvant anti-PD-1 in resected non-small-cell lung carcinoma: a proposal for quantitative immune-related pathologic response criteria (irPRC). Ann Oncol 2018;29:1853-60. [Crossref] [PubMed]