Experience with perioperative drug therapy in patients with stage III non-small cell lung cancer (results of the observational study CARL-001)

Introduction. The article considers approaches to the treatment of patients with stage III non-small-cell lung cancer (NSCLC). Particular attention is paid to neoadjuvant and adjuvant drug therapy.

Aim. To evaluate the efficacy of neoadjuvant treatments, such as neoadjuvant chemotherapy and immunochemotherapy, and adjuvant approaches to the stage III NSCLC treatment.

Materials and methods. The results were obtained during the study: Clinical Testing of Lung Cancer (“CARL-001”). A total of 186 untreated patients with stage IIIA-IIIC NSCLC (160 patients with stage IIIA, 25 patients with IIIB and 1 with IIIC) were enrolled in the study. The study included 108 patients with adenocarcinoma and 78 with squamous cell carcinoma. 118 patients underwent surgery with adjuvant polychemotherapy (aPCT), 49 patients underwent neoadjuvant polychemotherapy (neoPCT) followed by surgery, and 19 patients had neoadjuvant immunotherapy combined with chemotherapy (neoICT). The median follow-up was 40 months.

Results. Both adjuvant and neoadjuvant chemotherapy shared equivalent efficacy. The median relapse-free survival (RFS) in the aPCT and neoPCT groups was 30.4 and 32.6 months, respectively (differences between groups were not statistically significant). There was no significant difference in overall survival (OS) either. The use of neoICT showed better results as compared to neoPCT. The median RFS was not reached in the neoICT group, the median RFS in the neoPCT group was 32.6 months. OS was numerically higher in the neoICT group as compared to the neoPCT group, and accounted for 78.9% and 59.18% over a 36-month follow-up period, respectively.

Conclusions. Preoperative chemotherapy is proven to be equal to the postoperative chemotherapy in the treatment of patients with stage III NSCLC. The use of neoICT demonstrated better results as compared to neoPCT. Further study of these treatments will allow a more personalized approach to the treatment of patients with stage III NSCLC.

1. Thandra K, Barsouk A, Saginala K, Aluru J, Barsouk A. Epidemiology of lung cancer. Contemp Oncol. 2021;25(1):45-52. https://doi.org/10.5114/wo.2021.103829.

2. Kratzer T, Bandi P, Freedman N, Smith R, Travis W, Jemal A, Siegel R. Lung cancer statistics, 2023. Cancer. 2024;130(8):1330-1348. https://doi.org/10.1002/cncr.35128.

3. Casal-Mouriño A, Ruano-Ravina A, Lorenzo-González M, Rodríguez-Martínez Á, Giraldo-Osorio A, Varela-Lema L et al. Epidemiology of stage III lung cancer: frequency, diagnostic characteristics, and survival. Transl Lung Cancer Res. 2021;10(1):506-518. https://doi.org/10.21037/tlcr.2020.03.40.

4. Verfaillie S, Lambrecht M, Berkovic P, Dooms C, Nackaerts K, Van de Velde AS et al. Treatment of unresectable stage III NSCLC: Real world cohort study and literature review. Cancer Treat Res Commun. 2023;36:100727. https://doi.org/10.1016/j.ctarc.2023.100727.

5. Laktionov KK, Artamonova EV, Breder VV, Gorbunova VA, Demidova IA, Dengina NV et al. Practice guidelines for drug therapy of non-small cell lung cancer. Malignant Tumors. 2022;12(3):41-59. (In Russ.) https://doi.org/10.18027/2224-5057-2022-12-3s2-41-59.

6. Van Schil PE, Berzenji L, Yogeswaran SK, Hendriks JM, Lauwers P. Surgical Management of Stage IIIA Non-Small Cell Lung Cancer. Front Oncol. 2017;7:249. https://doi.org/10.3389/fonc.2017.00249.

7. Wu Y, Yang X, Zhong W, Wu Y, Yang X, Zhong W et al. Multi-centre randomized controlled study comparing adjuvant vs neo-adjuvant chemotherapy with docetaxel plus carboplatin in resectable stage IB to IIIA NSCLC: final results of CSLC0501. Ann Oncol. 2016;27(6 Suppl.):VI407. https://doi.org/10.1093/annonc/mdw381.01.

8. McElnay P, Lim E. Adjuvant or neoadjuvant chemotherapy for NSCLC. J Thorac Dis. 2014;6(2 Suppl.):S224-S227. https://doi.org/10.3978/j.issn.2072-1439.2014.04.26.

9. De Marinis F, Gebbia V, De Petris L. Neoadjuvant chemotherapy for stage IIIA-N2 non-small cell lung cancer. Ann Oncol. 2005;16(4 Suppl.):iv116-iv122. https://doi.org/10.1093/annonc/mdi920.

10. Song WA, Zhou NK, Wang W, Chu XY, Liang CY, Tian XD et al. Survival benefit of neoadjuvant chemotherapy in non-small cell lung cancer: an updated meta-analysis of 13 randomized control trials. J Thorac Oncol. 2010;5(4):510-516. https://doi.org/10.1097/JTO.0b013e3181cd3345.

11. Christopoulos P. The emerging perioperative treatment paradigm for nonsmall cell lung cancer: a narrative review. Chin Clin Oncol. 2024;13(1):12. https://doi.org/10.21037/cco-23-137.

12. Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatinbased adjuvant chemotherapy in patients with completely resected nonsmall-cell lung cancer. N Engl J Med. 2004;350(4):351-360. https://doi.org/10.1056/NEJMoa031644.

13. Pirker R. Adjuvant Chemotherapy of Non-Small Cell Lung Cancer. Tanaffos. 2012;11(1):12-17. Available at: https://pmc.ncbi.nlm.nih.gov/articles/ PMC4153177.

14. Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM et al.; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022;386(21):1973-1985. https://doi.org/10.1056/NEJMoa2202170.

15. Felip E, Altorki N, Vallieres E, Vynnychenko I, Akopov A, Martinez-Marti A et al. IMpower010: overall survival interim analysis of a phase III study of atezolizumab vs best supportive care in resected NSCLC. In: 2022 World Conference on Lung Cancer, August 6-9, 2022, Vienna, Austria. 2022. 12 p.

16. Zhang B, Xiao H, Pu X, Zhou C, Yang D, Li X et al. A real-world comparison between neoadjuvant chemoimmunotherapy and chemotherapy alone for resectable non-small cell lung cancer. Cancer Med. 2023;12(1):274-286. https://doi.org/10.1002/cam4.4889.

17. John AO, Ramnath N. Neoadjuvant Versus Adjuvant Systemic Therapy for Early-Stage Non-Small Cell Lung Cancer: The Changing Landscape Due to Immunotherapy. Oncologist. 2023;28(9):752-764. https://doi.org/10.1093/oncolo/oyad125.

18. Lee KY, Hsu CX. Adjuvant chemotherapy or immunotherapy for completely resected stage IB non-small cell lung cancer: still a grey zone? Transl Lung Cancer Res. 2023;12(3):647-648. https://doi.org/10.21037/tlcr-22-897.

19. Tang WF, Ye HY, Tang X, Su JW, Xu KM, Zhong WZ, Liang Y. Adjuvant immunotherapy in early-stage resectable non-small cell lung cancer: A new milestone. Front Oncol. 2023;13:1063183. https://doi.org/10.3389/fonc.2023.1063183.

20. Fergadis E, Heitmann A, Tsaras T, Hardavella G. Adjuvant immunotherapy and targeted therapy in early and locally advanced resectable lung cancer: expanding treatment tentacles? Breathe. 2024;20(2):240035. https://doi.org/10.1183/20734735.0035-2024.