NEOTIDE/CTONG2104：EGFR敏感突变NSCLC新辅助PD-1抑制剂联合化疗

Chao Zhang, Ben-Yuan Jiang, Li-Xu Yan, Li-Shan Peng, Jin-Hu Li, Zhi-Yong Chen, Yu-Xuan Sun, Jian Su, Ri-Qiang Liao, Song Dong, Hong-Hong Yan, Chong-Rui Xu, Qing Zhou, Xue-Ning Yang, Zheng Hu, Yi-Long Wu, Wen-Zhao Zhong,
Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant non-small cell lung cancer (NEOTIDE/CTONG2104): phase II trial and correlative genomic analysis in China,
eClinicalMedicine,Volume 96,2026,103994,ISSN 2589-5370,https://doi.org/10.1016/j.eclinm.2026.103994.(https://www.sciencedirect.com/sc ... i/S2589537026002427)
Background
To evaluate the efficacy and safety of neoadjuvant sintilimab, a programmed cell death 1 protein (PD-1) blockade combined with chemotherapy in patients with resectable stage II-IIIB epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC).
Methods
This was a single-arm, open-label, phase II trial (CTONG2104) conducted in China. Patients with resectable stage II-IIIB EGFR (AJCC 8th edition) mutant NSCLC were enroled and received neoadjuvant sintilimab (200 mg) plus carboplatin (area under the curve 5) and nab-paclitaxel (260 mg/m2) for 3 cycles. Patients in stage II cohort received adjuvant osimertinib for up to 2 years while observation for stage I cohort. The primary endpoint was major pathological response (MPR) rate (per IASLC criteria) in patients who received at least one dose neoadjuvant sintilimab plus chemotherapy. Secondary endpoints included pathological complete response (pCR) rate (per IASLC criteria), objective response (ORR) rate (per RECIST), event-free survival (EFS), overall survival (OS) and safety profile in all enroled patients. This study is registered with ClinicalTrials.gov, NCT05244213.
Findings
Between May 10, 2022, and March 20, 2024, 35 eligible patients (median [range] age, 60 [48–73] years; 18 [51.4%] female) were enroled and received neoadjuvant treatment and 33 (94.3%) completed surgical resection. The median follow-up was 33.7 months. The primary endpoint was met, with a MPR following neoadjuvant immunochemotherapy of 34.3% (95% CI 19.1–52.2). The ORR and pCR was 60.0% and 11.4%, respectively. Patients with RB1 or RBM10 co-mutations respond well to neoadjuvant immunochemotherapy while opposite for EGFR tyrosine kinase inhibitors (TKIs). The median EFS was not reached with 2-year EFS rate of 71.4% (95% CI 57.9–88.1%). The safety profile during neoadjuvant treatment was tolerable, with 29% of patients experiencing grade 3-4 adverse events. All patients underwent minimally-invasive surgery with 87.9% achieved R0 resection. 42.9% patients experienced local relapse and oligo-metastasis, respectively and 81.8% achieved objective response after receiving EGFR-TKIs.
Interpretation
Neoadjuvant sintilimab plus chemotherapy revealed encouraging clinical and pathological response with well tolerability in EGFR-mutant NSCLC. Upfront immunochemotherapy did not add sever immune toxicity or impact response rate to TKIs for adjuvant or first-line osimertinib. Further study with randomized controlled design is warranted to verified such treatment modality.
Funding
Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant non-small cell lung cancer (NEOTIDE/CTONG2104): phase II trial and correlative genomic analysis in China - ScienceDirect  


1.更新的EGFR突变人群免疫化疗新辅助MPR(34.1%)/pCR(11.4%)以及中位EFS数据(25.3m)，L858R相比19del具有相对更好response rate和survival；
2.不同新辅助治疗多队列genomic数据提示RB1或RBM10共突变更可能从免疫联合化疗模式中获益；
3.EGFR突变新辅助免疫化疗后主要以远处复发进展为主，且免疫化疗不影响复发后靶向治疗疗效及安全性，新辅化免序贯辅助Osi不会带来显著安全性问题，肝损较ADAURA队列增高但无显著性。

文献来源：

Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant NSCLC: Phase 2 trial interim results (NEOTIDE/CTONG2104)
Zhang C, Sun YX, Yi DC, Jiang BY, Yan LX, Liu ZD, Peng LS, Zhang WJ, Sun H, Chen ZY, Wang DH, Peng D, Chen SA, Li SQ, Zhang Z, Tan XY, Yang J, Zhao ZY, Zhang WT, Su J, Li YS, Liao RQ, Dong S, Xu CR, Zhou Q, Yang XN, Wu YL, Zhang ZM, Zhong WZ. Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant NSCLC: Phase 2 trial interim results (NEOTIDE/CTONG2104). Cell Rep Med. 2024 Jul 16;5(7):101615. doi: 10.1016/j.xcrm.2024.101615. Epub 2024 Jun 18. PMID: 38897205; PMCID: PMC11293361.
Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant NSCLC: Phase 2 trial interim results (NEOTIDE/CTONG2104): Cell Reports Medicine

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Study Details | Neoadjuvant Immunotherapy in EGFR-mutant Localized NSCLC | ClinicalTrials.gov
Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant NSCLC: Phase 2 trial interim results (NEOTIDE/CTONG2104) - PubMed (nih.gov)
Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant NSCLC: Phase 2 trial interim results (NEOTIDE/CTONG2104) - ScienceDirect
Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant NSCLC: Phase 2 trial interim results (NEOTIDE/CTONG2104) (cell.com)
176.… | The American Association for Thoracic Surgery | AATS