- Department of oncology surgery, Shanghai Chest Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200030, P. R. China;
LUO Qingquan,
Email: luoqingquan@hotmail.com
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Although surgery can cure some early-stage resectable patients, the postoperative recurrence rate remains as high as 30%-55%. Perioperative immune checkpoint inhibitor (ICI) therapy, which includes "neoadjuvant" therapy before surgery and "adjuvant" therapy after surgery, has significantly improved survival outcomes in resectable NSCLC patients. Large clinical studies, such as CheckMate 816, have demonstrated the superiority of neoadjuvant ICIs combined with chemotherapy in increasing the pathological complete response rate (pCR) and prolonging event-free survival (EFS). However, even with these advanced treatments, some patients do not achieve long-term benefits and experience early recurrence. This paper reviews the latest research progress of perioperative ICIs in NSCLC treatment, particularly the effectiveness of neoadjuvant chemoimmunotherapy in improving pCR and extending EFS. It further explores the recurrence patterns, resistance mechanisms, and potential biomarkers in NSCLC patients after neoadjuvant immunotherapy. By integrating basic research and clinical data, we analyze the mechanisms of early recurrence following perioperative immunotherapy and discuss future research directions and therapeutic strategies, providing new insights into precision treatment and recurrence prevention for NSCLC patients.
Copyright © the editorial department of Chinese Journal of Clinical Thoracic and Cardiovascular Surgery of West China Medical Publisher. All rights reserved
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- 2. Taylor MD, Nagji AS, Bhamidipati CM, et al. Tumor recurrence after complete resection for non-small cell lung cancer. Ann Thorac Surg, 2012, 93(6): 1813-1821.
- 3. Uramoto H, Tanaka F. Recurrence after surgery in patients with nsclc. Translational lung cancer research, 2014, 3(4): 242.
- 4. Ettinger DS, Wood DE, Aisner DL, et al. Non–small cell lung cancer, version 3. 2022, nccn clinical practice guidelines in oncology. J Natl Comprehensive Canr Net, 2022, 20(5): 497-530.
- 5. Pignon JP, Tribodet H, Scagliotti GV, et al. Lung adjuvant cisplatin evaluation: A pooled analysis by the lace collaborative group. J Clin Oncol, 2008, 26(21): 3552-3559.
- 6. 中国抗癌协会肺癌专业委员会, 中华医学会肿瘤学分会肺癌学组, 中国胸部肿瘤研究协作组, 等. Ⅰ~Ⅲb期非小细胞肺癌完全切除术后辅助治疗指南(2021版). 中华医学杂志, 2021, 101(16): 11.China Anti Cancer Association Lung Cancer Professional Committee, Chinese Medical Association Oncology Branch Lung Cancer Group, China Chest Tumor Research Collaboration Group, etc Guidelines for adjuvant therapy after complete resection of stage I-IIIb non-small cell lung cancer (2021 edition). Natl Med J China, 2021, 101(16): 11.
- 7. Group N M-a C. Preoperative chemotherapy for non-small-cell lung cancer: A systematic review and meta-analysis of individual participant data. Lancet, 2014, 383(9928): 1561-1571.
- 8. Felip E, Altorki N, Zhou C, et al. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage Ⅰb–Ⅲa non-small-cell lung cancer (impower010): A randomised, multicentre, open-label, phase 3 trial. The Lancet, 2021, 398(10308): 1344-1357.
- 9. O’brien M, Paz-Ares L, Marreaud S, et al. Pembrolizumab versus placebo as adjuvant therapy for completely resected stage ib–Ⅲa non-small-cell lung cancer (pearls/keynote-091): An interim analysis of a randomised, triple-blind, phase 3 trial. The Lancet Oncology, 2022, 23(10): 1274-1286.
- 10. Forde PM, Chaft E, Smith KN, et al. Neoadjuvant pd-1 blockade in resectable lung cancer. NEJM, 2018, 378(21): 1976-1986.
- 11. Forde PM, Spicer J, Lu S, et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. NEJM, 2022, 386(21): 1973-1985.
- 12. Akinboro O, Drezner N, Amatya A, et al. Us food and drug administration approval summary: Nivolumab plus platinum-doublet chemotherapy for the neoadjuvant treatment of patients with resectable non–small-cell lung cancer. J Clin Oncol, 2023, 41(17): 3249-3259.
- 13. Spicer J, Girard N, Provencio M, et al. Neoadjuvant nivolumab (nivo) + hemotherapy (chemo) vs chemo in patients (pts) with resectable nsclc: 4-year update from checkmate 816. Journal of Clinical Oncology, 2024, 42(17_suppl): LBA8010-LBA8010.
- 14. Altorki N K, Walsh Z H, Melms J C, et al. Neoadjuvant durvalumab plus radiation versus durvalumab alone in stages Ⅰ–Ⅲ non-small cell lung cancer: Survival outcomes and molecular correlates of a randomized phase Ⅱ trial. Nature Communications, 2023, 14(1): 8435.
- 15. Provencio M, Nadal E, Insa A, et al. Neoadjuvant chemotherapy and nivolumab in resectable non-small-cell lung cancer (nadim): An open-label, multicentre, single-arm, phase 2 trial. The Lancet Oncology, 2020, 21(11): 1413-1422.
- 16. Provencio M, Serna-Blasco R, Nadal E, et al. Overall survival and biomarker analysis of neoadjuvant nivolumab plus chemotherapy in operable stage Ⅲa non–small-cell lung cancer (nadim phase Ⅱ trial). J Clin Oncol, 2022, 40(25): 2924-2933.
- 17. Cascone T, Awad MM, Spicer JD, et al. Perioperative nivolumab in resectable lung cancer. NEJM, 2024, 390(19): 1756-1769.
- 18. Heymach J V, Harpole D, Mitsudomi T, et al. Perioperative durvalumab for resectable non–small-cell lung cancer. NEJM, 2023, 389(18): 1672-1684.
- 19. Lu S, Zhang W, Wu L, et al. Perioperative toripalimab plus chemotherapy for patients with resectable non–small cell lung cancer: The neotorch randomized clinical trial. JAMA, 2024, 331(3): 201-211.
- 20. Potter AL, Costantino CL, Suliman RA, et al. Recurrence after complete resection for non-small cell lung cancer in the national lung screening trial. Ann Thorac Surg, 2023, 116(4): 684-692.
- 21. Pan H, Chen H, Kong W, et al. Video-assisted thoracoscopic surgery versus thoracotomy following neoadjuvant immunochemotherapy in resectable stage Ⅲ non-small cell lung cancer among chinese populations: A multi-center retrospective cohort study. Clin Lung Cancer, 2024.
- 22. Tian Y, Liu Z, Pan H, et al. Perioperative immune checkpoint blockades improve prognosis of resectable non-small cell lung cancer. Eur JCardio-Thorac Surg, 2024, 65(4): .
- 23. Mountzios G, Remon J, Hendriks LE, et al. Immune-checkpoint inhibition for resectable non-small-cell lung cancer—opportunities and challenges. Nat Rev Clin Oncol, 2023, 20(10): 664-677.
- 24. Chen D S, Mellman I. Oncology meets immunology: The cancer-immunity cycle. Immunity, 2013, 39(1): 1-10.
- 25. Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell, 2011, 144(5): 646-674.
- 26. Kluger HM, Tawbi HA, Ascierto ML, et al. Defining tumor resistance to PD-1 pathway blockade: Recommendations from the first meeting of the sitc immunotherapy resistance taskforce. J Immunother Cancer, 2020, 8(1).
- 27. Passaro A, Brahmer J, Antonia S, et al. Managing resistance to immune checkpoint inhibitors in lung cancer: Treatment and novel strategies. J Clinl Oncol, 2022, 40(6): 598-610.
- 28. Sharma P, Hu-Lieskovan S, Wargo J A, et al. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell, 2017, 168(4): 707-723.
- 29. Aldea M, Andre F, Marabelle A, et al. Overcoming resistance to tumor-targeted and immune-targeted therapies. Cancer Discov, 2021, 11(4): 874-899.
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