Interpretation of advances in the treatment of non-small cell lung cancer at the 2025 World Conference on Lung Cancer (WCLC)_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

BAO Bo ^1,2 , LU Jiayu ¹ , LIU Wen ^1,2 , ZHANG Xuxu ² , LI Jiahe ² , ZHANG Jipeng ² , LI Wei ² ,  LU Qiang ²

1. Basic Medical College, Air Force Medical University, Xi'an, 710032, P. R. China;
2. Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, 710038, P. R. China;

Corresponding?author：

LU Qiang, Email: luqiang@fmmu.edu.cn

Keywords：

World Conference on Lung Cancer; non-small cell lung cancer; targeted therapy; immunotherapy; epidermal growth factor receptor; drug resistance; antibody-drug conjugates; interpretation

DOI：

10.7507/1007-4848.202510060

Video：

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The 26th World Conference on Lung Cancer (WCLC) was held in Barcelona during September 6-9, 2025. As the world's largest and most influential academic meeting in the field of lung cancer, this year's congress unveiled long-term follow-up data from several pivotal studies and significant advances in novel therapeutic strategies. In the realm of targeted therapy, a next-generation combination strategy has been established as the new standard of care for the first-line treatment of patients with advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), demonstrating a significant improvement in overall survival. In immunotherapy, novel combination regimens have not only addressed the therapeutic challenge of acquired resistance to EGFR targeted therapies, but also shown clear long-term survival benefits in both the perioperative and locally advanced settings. These findings pave the way for shifting the treatment paradigm to earlier stages for patients with NSCLC. Antibody-drug conjugates have made remarkable strides in this field. They have shown outstanding efficacy in patients with specific resistance mutations and those with brain metastases, and have also demonstrated immense potential in treating patients with HER2-aberrant lung cancer and broader NSCLC populations. This offers new therapeutic options for patients with refractory lung cancer.However, significant challenges remain, including the heterogeneity of resistance mechanisms, the selection of optimal treatment regimens, and management strategies for special populations. Future research should focus on identifying novel precision biomarkers and optimizing therapeutic strategies to ultimately improve clinical outcomes for all patients with lung cancer.

Citation： BAO Bo, LU Jiayu, LIU Wen, ZHANG Xuxu, LI Jiahe, ZHANG Jipeng, LI Wei, LU Qiang. Interpretation of advances in the treatment of non-small cell lung cancer at the 2025 World Conference on Lung Cancer (WCLC). Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2026, 33(2): 218-230. doi: 10.7507/1007-4848.202510060 Copy

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1. Shi Y, Xing L, Zhang Z, et al. MA08.06 Comparison of asandeutertinib and osimertinib in EGFR-mutated NSCLC with brain metastases: interim analysis of the ESAONA pivotal study. J Thorac Oncol, 2025, 20(10 Suppl 1): S89-S90.
2. Jeon H, Wang S, Song J, et al. Update 2025: management of non-small-cell lung cancer. Lung, 2025, 203(1): 53.
3. Chevallier M, Borgeaud M, Addeo A, et al. Oncogenic driver mutations in non-small cell lung cancer: past, present and future. World J Clin Oncol, 2021, 12(4): 217-237.
4. Moyer JD, Barbacci EG, Iwata KK, et al. Induction of apoptosis and cell cycle arrest by CP-358, 774, an inhibitor of epidermal growth factor receptor tyrosine kinase. Cancer Res, 1997, 57(21): 4838-4848.
5. Barker AJ, Gibson KH, Grundy W, et al. Studies leading to the identification of ZD1839 (IRESSA): an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor targeted to the treatment of cancer. Bioorg Med Chem Lett, 2001, 11(14): 1911-1914.
6. Meertens M, de Jong LD, de Vries N, et al. LC-MS/MS method development and validation for novel targeted anticancer therapies adagrasib, capmatinib, ensartinib, entrectinib, larotrectinib, lorlatinib, pralsetinib, selpercatinib and sotorasib. J Pharm Biomed Anal, 2025, 266: 117078.
7. 中國臨床腫瘤學會指南工作委員會. 中國臨床腫瘤學會(CSCO)非小細胞肺癌診療指南. 2025版. 北京: 人民衛生出版社, 2025.Guidelines Committee of Chinese Society of Clinical Oncology. Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Non-small Cell Lung Cancer. 2025 ed. Beijing: People's Medical Publishing House, 2025.
8. Wang J, Wang ZJ, Zhong J, et al. PL02.09 Aumolertinib plus chemotherapy for NSCLC with EGFR and concomitant tumor suppressor genes (ACROSS 2): phase Ⅲ study. J Thorac Oncol, 2025, 20(10 Suppl 1): S1-S2.
9. Borgeaud M, Olivier T, Bar J, et al. Personalized care for patients with EGFR-mutant nonsmall cell lung cancer: navigating early to advanced disease management. CA Cancer J Clin, 2025, 75(5): 387-409.
10. Zhao J, Xu W, Zhou F, et al. Navigating the landscape of EGFR TKI resistance in EGFR-mutant NSCLC: mechanisms and evolving treatment approaches. Nat Rev Clin Oncol, 2026, 23(1): 63-83.
11. J?nne PA, Planchard D, Kobayashi K, et al. A plain language summary of results from the FLAURA2 study: effects of initial (first-line) osimertinib plus chemotherapy on the brain in patients with EGFR-mutated advanced non-small cell lung cancer. Future Oncol, 2025, 21(8): 917-928.
12. Ahmed S, Yang JC, Kobayashi K, et al. P3.12. 65 First-line osimertinib±platinum-pemetrexed in EGFR-mutated advanced NSCLC: FLAURA2 clinical outcomes by EGFRm subtype. J Thorac Oncol, 2025, 20(10 Suppl 1): S498.
13. Gerber DE, Wang Y, Langer CJ, et al. PL02.18 Phase 3 trial of crizotinib vs observation for surgically resected early-stage ALK+ NSCLC. J Thorac Oncol, 2025, 20(10 Suppl 1): S4.
14. NSCLC Meta-analysis Collaborative Group. Preoperative chemotherapy for non-small-cell lung cancer: a systematic review and meta-analysis of individual participant data. Lancet, 2014, 383(9928): 1561-1571.
15. Zhai H, Zhong W, Yang X, et al. Neoadjuvant and adjuvant epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy for lung cancer. Transl Lung Cancer Res, 2015, 4(1): 82-93.
16. He J, Tsuboi M, Weder W, et al. Neoadjuvant osimertinib for resectable EGFR-mutated non-small cell lung cancer. J Clin Oncol, 2025, 43(26): 2875-2887.
17. Cross DA, Ashton SE, Ghiorghiu S, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov, 2014, 4(9): 1046-1061.
18. Tsuboi M, Herbst RS, John T, et al. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med, 2023, 389(2): 137-147.
19. Peled N, Tufman A, Sequist LV, et al. COMPEL: osimertinib plus platinum-based chemotherapy in patients with EGFR-mutated advanced NSCLC and progression on first-line osimertinib. ESMO Open, 2025, 10: 105807.
20. Zhou Q, Zhao H, Lu S, et al. Consensus on the lung cancer management after third-generation EGFR-TKI resistance. Lancet Reg Health West Pac, 2024, 53: 101260.
21. Reita D, Pabst L, Pencreach E, et al. Molecular mechanism of EGFR-TKI resistance in EGFR-mutated non-small cell lung cancer: application to biological diagnostic and monitoring. Cancers (Basel), 2021, 13(19): 4926.
22. Fang W, Zhao Y, Luo Y, et al. Ivonescimab plus chemotherapy in non-small cell lung cancer with EGFR variant: a randomized clinical trial. JAMA, 2024, 332(7): 561-570.
23. Zhang L, Fang W, Li X, et al. Sacituzumab tirumotecan (sac-TMT) in patients (pts) with previously treated advanced EGFR-mutated non-small cell lung cancer (NSCLC): results from the randomized OptiTROP-Lung03 study. J Clin Oncol, 2025, 43(16 Suppl): 8507.
24. Yang J, Li A, Feng WN, et al. PL04.10 Osimertinib with or without savolitinib as 1L in de novo MET aberrant, EGFRm advanced NSCLC (CTONG 2008): a phase Ⅱ trial. J Thorac Oncol, 2024, 19(10 Suppl): S6.
25. Yang JC, Lu S, Hayashi H, et al. Overall survival with amivantamab-lazertinib in EGFR-mutated advanced NSCLC. N Engl J Med, 2025, 393(17): 1681-1693.
26. Cho BC, Lu S, Felip E, et al. Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC. N Engl J Med, 2024, 391(16): 1486-1498.
27. Le X, Patel JD, Shum E, et al. A multicenter open-label randomized phase II study of osimertinib with and without ramucirumab in tyrosine kinase inhibitor-na?ve EGFR-mutant metastatic non-small cell lung cancer (RAMOSE trial). J Clin Oncol, 2025, 43(4): 403-411.
28. Levy BP, de Marinis F, Bonanno L, et al. Efficacy and CNS results from a randomized subset of the phase 2 SAVANNAH study comparing savolitinib (savo)+osimertinib (osi) combination with savo+placebo (PBO). J Clin Oncol, 2025, 43(16 Suppl): 8513.
29. Baik C, de Marinis F, Bonanno L, et al. MA03.03 SAVANNAH: biomarker concordance and acquired resistance in patients with EGFRm MET-overexp and/or amp NSCLC. J Thorac Oncol, 2025, 20(10 Suppl 1): S61-S62.
30. Novello S, de Marinis F, Kim TM, et al. PT2.12. 04 Osimertinib+savolitinib in EGFRm advanced NSCLC with MET overexp and/or amp post-progression on osimertinib: SAVANNAH PROs. J Thorac Oncol, 2025, 20(10 Suppl 1): S614-S615.
31. Lu S, Wang J, Yang N, et al. Savolitinib (savo) combined with osimertinib (osi) versus chemotherapy (chemo) in EGFR-mutant (EGFRm) and MET-amplification (METamp) advanced NSCLC after disease progression (PD) on EGFR tyrosine kinase inhibitor (TKI): results from a randomized phase 3 SACHI study. J Clin Oncol, 2025, 43(17 Suppl): LBA8505.
32. Spicer JD, Provencio Pulla M, Cascone T, et al. MA04.05 Patient-reported outcomes with perioperative nivolumab by nodal status in patients with resectable NSCLC from Checkmate 77T. J Thorac Oncol, 2025, 20(10 Suppl 1): S67-S68.
33. Wakelee H, Demedts I, Langleben A, et al. MA04.04 Perioperative pembrolizumab in non-small cell cancer (NSCLC): 4-year outcomes by nodal status in the KEYNOTE-671 study. J Thorac Oncol, 2025, 20(10 Suppl 1): S67.
34. Mitsudomi T, Forde PM, Girard N, et al. OA02.03 Overall survival (OS) with neoadjuvant nivolumab plus chemotherapy by surgical outcomes in the phase 3 CheckMate 816 study. J Thorac Oncol, 2025, 20(10 Suppl 1): S13.
35. Spigel DR, Faivre-Finn C, Gray JE, et al. Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage Ⅲ non-small-cell lung cancer. J Clin Oncol, 2022, 40(12): 1301-1311.
36. Varlotto JM, Xie Y, Pennell N, et al. PL03.06 EA5181: phase 3 trial of concurrent and consolidative durvalumab vs consolidation durva alone for unresectable stage 3 NSCLC. J Thorac Oncol, 2025, 20(10 Suppl 1): S4-S5.
37. Pass H, Felip E, Shu CA, et al. OA02.01 SKYSCRAPER-05: phase Ⅱ study of perioperative tiragolumab+atezolizumab±chemotherapy in locally advanced resectable NSCLC. J Thorac Oncol, 2025, 20(10 Suppl 1): S11-S12.
38. Di Federico A, Alden SL, Smithy JW, et al. Intrapatient variation in PD-L1 expression and tumor mutational burden and the impact on outcomes to immune checkpoint inhibitor therapy in patients with non-small-cell lung cancer. Ann Oncol, 2024, 35(10): 902-913.
39. Boukouris AE, Michaelidou K, Joosse SA, et al. A comprehensive overview of minimal residual disease in the management of early-stage and locally advanced non-small cell lung cancer. NPJ Precis Oncol, 2025, 9(1): 178.
40. Isbell JM, Goldstein JS, Hamilton EG, et al. Ultrasensitive circulating tumor DNA (ctDNA) minimal residual disease (MRD) detection in early stage non-small cell lung cancer (NSCLC). J Clin Oncol, 2024, 42(16 Suppl): 8078.
41. Itatani Y, Kawada K, Yamamoto T, et al. Resistance to anti-angiogenic therapy in cancer-alterations to anti-VEGF pathway. Int J Mol Sci, 2018, 19(4): 1232.
42. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med, 2006, 355(24): 2542-2550.
43. Xiong A, Wang L, Chen J, et al. Ivonescimab versus pembrolizumab for PD-L1-positive non-small cell lung cancer (HARMONi-2): a randomised, double-blind, phase 3 study in China. Lancet, 2025, 405(10481): 839-849.
44. Xue M, Jin W. Ivonescimab versus pembrolizumab in PD-L1-positive NSCLC. Lancet, 2025, 406(10510): 1336-1337.
45. Felip E, Rojas CI, Schenker M, et al. Subcutaneous versus intravenous pembrolizumab, in combination with chemotherapy, for treatment of metastatic non-small-cell lung cancer: the phase Ⅲ 3475A-D77 trial. Ann Oncol, 2025, 36(7): 775-785.
46. Wang L, Wu L, Yao J, et al. P1.11. 65 Ivonescimab versus pembrolizumab for PD-L1-positive NSCLC: a subgroup analysis of HARMONi-2 by tumor PD-L1 expression level. J Thorac Oncol, 2025, 20(10 Suppl 1): S197-S198.
47. Xiong A, Chen J, Liu B, et al. P1.11. 83 Ivonescimab versus pembrolizumab for PD-L1-positive NSCLC: a subgroup analysis of HARMONi-2 by tumor histology. J Thorac Oncol, 2025, 20(10 Suppl 1): S206-S207.
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Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Interpretation of advances in the treatment of non-small cell lung cancer at the 2025 World Conference on Lung Cancer (WCLC)

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