Efficacy comparison of first-line <i>versus</i> subsequent-line immunotherapy in extensive-stage small cell lung cancer_West China Medical Journal

Authors：

FAN Ting ^1,2 , YUAN Haiting ² , LIN Wuhua ² , LIU Yanyang ¹ , LI Junqing ² ,  ZHANG Yan ²

1. Lung Cancer Center / Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, Sichuan 611135, P. R. China;
2. Department of Armed Police Forces Hospital of Sichuan, Leshan, Sichuan 614000, P. R. China;

Corresponding?author：

ZHANG Yan, Email: zhang.yan@scu.edu.cn

Keywords：

Extensive-stage small cell lung cancer; immunotherapy; prognosis

DOI：

10.7507/1002-0179.202502182

Video：

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Objective To compare the efficacy differences of immune checkpoint inhibitors (ICIs) in first-line versus subsequent-line immunotherapy for extensive-stage small-cell lung cancer (ES-SCLC). Methods Data on patients diagnosed with small cell lung cancer (SCLC) between January 2021 and December 2023 were retrospectively collected from West China Hospital of Sichuan University. According to the time at which ICIs were used, patients were divided into first-line immunotherapy group and subsequent-line immunotherapy group. Multivariate Cox proportional hazards regression model analysis was used to analyze the influencing factors of overall survival (OS). Results A total of 166 patients were included. Among them, there were 121 cases in the first-line immunotherapy group and 45 cases in the subsequent-line immunotherapy group. The median follow-up lasted for 24.07 (16.27, 31.70) months. Fifty-three patients died in the first-line immunotherapy group and 28 in the subsequent-line immunotherapy group. The median OS of the two groups was 28.6 and 16.2 months, respectively, and the difference was statistically significant (log-rank P=0.021). There was also a significant difference in time to disease progression free survival between the two groups (9.67 and 7.90 months, respectively; log-rank P=0.008). There was no difference in OS between patients who continued and those who did not continue an ICI-containing regimen after disease progression on first-line immunotherapy (median OS of 37.1 and 24.8 months for continuation of immunotherapy versus no immunotherapy, respectively; log-rank P=0.600). Multivariate Cox regression analysis found that body mass index≥24 kg/m² (P=0.014) and undergoing prophylactic cranial irradiation (P=0.036) reduced the risk of death. Conclusions ES-SCLC patients with first-line initial therapy using ICIs-containing drugs had better OS than those with ICIs in the subsequent-line, and re-selection of the same or different ICIs after progression of those who had used ICIs drugs in the first line did not improve survival.

Citation： FAN Ting, YUAN Haiting, LIN Wuhua, LIU Yanyang, LI Junqing, ZHANG Yan. Efficacy comparison of first-line versus subsequent-line immunotherapy in extensive-stage small cell lung cancer. West China Medical Journal, 2025, 40(12): 1936-1942. doi: 10.7507/1002-0179.202502182 Copy

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2.	Chen T, Wang M, Chen Y, et al. Advances in predictive biomarkers associated with immunotherapy in extensive-stage small cell lung cancer. Cell Biosci, 2024, 14(1): 117.
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4.	Rudin CM, Brambilla E, Faivre-Finn C, et al. Small-cell lung cancer. Nat Rev Dis Primers, 2021, 7(1): 3.
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12.	Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med, 2016, 375(19): 1823-1833.
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14.	Qiu G, Wang F, Xie X, et al. A retrospective real-world experience of immunotherapy in patients with extensive stage small-cell lung cancer. Cancer Med, 2023, 12(14): 14881-14891.
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16.	Li L, Liu T, Liu Q, et al. Rechallenge of immunotherapy beyond progression in patients with extensive-stage small-cell lung cancer. Front Pharmacol, 2022, 13: 967559.
17.	Yang Y, Ai X, Xu H, et al. Treatment patterns and outcomes of immunotherapy in extensive-stage small-cell lung cancer based on real-world practice. Thorac Cancer, 2022, 13(23): 3295-3303.
18.	Riihim?ki M, Hemminki A, Fallah M, et al. Metastatic sites and survival in lung cancer. Lung Cancer, 2014, 86(1): 78-84.
19.	Liu L, Liu T, Wang X, et al. Patterns of treatment failure for PD-(L)1 refractory extensive-stage small cell lung cancer in continued PD-(L)1 treatment. Transl Oncol, 2023, 33: 101687.
20.	Lin Y, Jiang W, Su CY, et al. Impact of liver metastases status on survival outcomes of first-line immunotherapy in extensive stage small cell lung cancer: a systematic review and meta-analysis. Aging (Albany NY), 2023, 15(18): 9561-9571.
21.	Fan L, Lin Y, Fu Y, et al. Small cell lung cancer with liver metastases: from underlying mechanisms to treatment strategies. Cancer Metastasis Rev, 2024, 44(1): 5.
22.	Gross AJ, Sheikh S, Kharouta M, et al. The impact of prophylactic cranial irradiation and consolidative thoracic radiation therapy for extensive stage small-cell lung cancer in the transition to the chemo-immunotherapy era: a single institution series. Clin Lung Cancer, 2023, 24(8): 696-705.
23.	Slotman BJ, van Tinteren H, Praag JO, et al. Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase3 randomised controlled trial. Lancet, 2015, 385(9962): 36-42.
24.	Cozzi S, Bruni A, Ruggieri MP, et al. Thoracic radiotherapy in extensive disease small cell lung cancer: multicenter prospective observational TRENDS study. Cancers (Basel), 2023, 15(2): 434.
25.	Fang M, Wang L, Gu Q, et al. Efficacy and safety of thoracic radiotherapy for extensive stage small cell lung cancer after immunotherapy in real world. Clin Exp Metastasis, 2023, 40(5): 423-429.
26.	Yao Y, Li B, Song R, et al. Efficacy and safety of thoracic radiotherapy in extensive-stage small-cell lung cancer patients receiving first-line immunotherapy plus chemotherapy:a propensity score matched multicentre retrospective analysis. Radiat Oncol, 2024, 19(1): 25.
27.	Chen D, Zou B, Li B, et al. Adebrelimab plus chemotherapy and sequential thoracic radiotherapy as first-line therapy for extensive-stage small-cell lung cancer (ES-SCLC): a phase II trial. EClinicalMedicine, 2024, 75: 102795.
28.	Wang H, Yao Z, Kang K, et al. Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer. Med, 2024, 5(10): 1237-1254. e9.
29.	Tian L, Huang JX, Wan R, et al. Association between sarcopenia, clinical outcomes, and survival in patients with extensive-stage small cell lung cancer treated with first-line immunochemotherapy: a prospective cohort study. Nutr Cancer, 2025, 77(1): 62-69.
30.	李琛, 向世強. 基于炎癥指標和營養指標構建微波消融聯合免疫治療的晚期非小細胞肺癌患者預后列線圖模型. 數理醫藥學雜志, 2024, 37(12): 899-911.

1. Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022. CA Cancer J Clin, 2022, 72(1): 7-33.
2. Chen T, Wang M, Chen Y, et al. Advances in predictive biomarkers associated with immunotherapy in extensive-stage small cell lung cancer. Cell Biosci, 2024, 14(1): 117.
3. Lee JH, Saxena A, Giaccone G. Advancements in small cell lung cancer. Semin Cancer Biol, 2023, 93: 123-128.
4. Rudin CM, Brambilla E, Faivre-Finn C, et al. Small-cell lung cancer. Nat Rev Dis Primers, 2021, 7(1): 3.
5. Horn L, Mansfield AS, Szcz?sna A, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med, 2018, 379(23): 2220-2229.
6. Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum–etoposide versus platinum–etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet, 2019, 394(10212): 1929-1939.
7. Cheng Y, Han L, Wu L, et al. Effect of first-line serplulimab vs placebo added to chemotherapy on survival in patients with extensive-stage small cell lung cancer: the ASTRUM-005 randomized clinical trial. JAMA, 2022, 328(12): 1223-1232.
8. Cheng Y, Fan Y, Zhao Y, et al. Tislelizumab plus platinum and etoposide versus placebo plus platinum and etoposide as first-line treatment for extensive-stage SCLC (RATIONALE-312):a multicenter, double-blind, placebo-controlled, randomized, phase 3 clinical trial. J Thorac Oncol, 2024, 19(7): 1073-1085.
9. Cheng Y, Zhang W, Wu L, et al. Toripalimab plus chemotherapy as a first-line therapy for extensive-stage small cell lung cancer: the phase 3 EXTENTORCH randomized clinical trial. JAMA Oncol, 2025, 11(1): 16-25.
10. Antonia SJ, López-Martin JA, Bendell J, et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol, 2016, 17(7): 883-895.
11. Chung HC, Piha-Paul SA, Lopez-Martin J, et al. Pembrolizumab after two or more lines of previous therapy in patients with recurrent or metastatic SCLC: results from the KEYNOTE-028 and KEYNOTE-158 studies. J Thorac Oncol, 2020, 15(4): 618-627.
12. Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med, 2016, 375(19): 1823-1833.
13. Reck M, Rodríguez-Abreu D, Robinson AG, et al. Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol, 2019, 37(7): 537-546.
14. Qiu G, Wang F, Xie X, et al. A retrospective real-world experience of immunotherapy in patients with extensive stage small-cell lung cancer. Cancer Med, 2023, 12(14): 14881-14891.
15. Rittberg R, Leung B, Al-Hashami Z, et al. Real-world eligibility for platinum doublet plus immune checkpoint inhibitors in extensive-stage small-cell lung cancer. Front Oncol, 2022, 12: 1002385.
16. Li L, Liu T, Liu Q, et al. Rechallenge of immunotherapy beyond progression in patients with extensive-stage small-cell lung cancer. Front Pharmacol, 2022, 13: 967559.
17. Yang Y, Ai X, Xu H, et al. Treatment patterns and outcomes of immunotherapy in extensive-stage small-cell lung cancer based on real-world practice. Thorac Cancer, 2022, 13(23): 3295-3303.
18. Riihim?ki M, Hemminki A, Fallah M, et al. Metastatic sites and survival in lung cancer. Lung Cancer, 2014, 86(1): 78-84.
19. Liu L, Liu T, Wang X, et al. Patterns of treatment failure for PD-(L)1 refractory extensive-stage small cell lung cancer in continued PD-(L)1 treatment. Transl Oncol, 2023, 33: 101687.
20. Lin Y, Jiang W, Su CY, et al. Impact of liver metastases status on survival outcomes of first-line immunotherapy in extensive stage small cell lung cancer: a systematic review and meta-analysis. Aging (Albany NY), 2023, 15(18): 9561-9571.
21. Fan L, Lin Y, Fu Y, et al. Small cell lung cancer with liver metastases: from underlying mechanisms to treatment strategies. Cancer Metastasis Rev, 2024, 44(1): 5.
22. Gross AJ, Sheikh S, Kharouta M, et al. The impact of prophylactic cranial irradiation and consolidative thoracic radiation therapy for extensive stage small-cell lung cancer in the transition to the chemo-immunotherapy era: a single institution series. Clin Lung Cancer, 2023, 24(8): 696-705.
23. Slotman BJ, van Tinteren H, Praag JO, et al. Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase3 randomised controlled trial. Lancet, 2015, 385(9962): 36-42.
24. Cozzi S, Bruni A, Ruggieri MP, et al. Thoracic radiotherapy in extensive disease small cell lung cancer: multicenter prospective observational TRENDS study. Cancers (Basel), 2023, 15(2): 434.
25. Fang M, Wang L, Gu Q, et al. Efficacy and safety of thoracic radiotherapy for extensive stage small cell lung cancer after immunotherapy in real world. Clin Exp Metastasis, 2023, 40(5): 423-429.
26. Yao Y, Li B, Song R, et al. Efficacy and safety of thoracic radiotherapy in extensive-stage small-cell lung cancer patients receiving first-line immunotherapy plus chemotherapy:a propensity score matched multicentre retrospective analysis. Radiat Oncol, 2024, 19(1): 25.
27. Chen D, Zou B, Li B, et al. Adebrelimab plus chemotherapy and sequential thoracic radiotherapy as first-line therapy for extensive-stage small-cell lung cancer (ES-SCLC): a phase II trial. EClinicalMedicine, 2024, 75: 102795.
28. Wang H, Yao Z, Kang K, et al. Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer. Med, 2024, 5(10): 1237-1254. e9.
29. Tian L, Huang JX, Wan R, et al. Association between sarcopenia, clinical outcomes, and survival in patients with extensive-stage small cell lung cancer treated with first-line immunochemotherapy: a prospective cohort study. Nutr Cancer, 2025, 77(1): 62-69.
30. 李琛, 向世強. 基于炎癥指標和營養指標構建微波消融聯合免疫治療的晚期非小細胞肺癌患者預后列線圖模型. 數理醫藥學雜志, 2024, 37(12): 899-911.

West China Medical Journal

Efficacy comparison of first-line versus subsequent-line immunotherapy in extensive-stage small cell lung cancer

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