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Published in: Journal of Cancer Research and Clinical Oncology 2/2021

01-02-2021 | Lung Cancer | Original Article – Clinical Oncology

Efficacy and safety of immune checkpoint inhibitors (ICIs) in extensive-stage small cell lung cancer (SCLC)

Authors: Xiaoting Ma, Shan Wang, Yujian Zhang, Huamin Wei, Jing Yu

Published in: Journal of Cancer Research and Clinical Oncology | Issue 2/2021

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Abstract

Background

To evaluate the efficacy and safety of an immune checkpoint inhibitor (ICI) combined with chemotherapy in patients with advanced SCLC.

Methods

We searched published randomized-controlled trials (RCTs) to compare the effect of ICIs combined with chemotherapy and chemotherapy alone on SCLC. The extracted data included the number of people who achieved an objective response rate (ORR), the disease control rate (DCR), the hazard ratio (HR) of progression-free survival (PFS), and the overall survival (OS) with 95% confidence intervals (95% CI).

Results

Six RCTs involving 2477 patients were included. Compared with chemotherapy alone, patients receiving an ICI combined with chemotherapy had a significantly longer PFS (HR, 0.91; 95% CI 0.88–0.95, p < 0.00001) and OS (HR 0.92; 95% CI 0.89–0.96, p = 0.0001). The ORR increased, but the difference was not statistically significant (RR 1.05; 95% CI 0.99–1.12, p = 0.13). There was no significant difference in the DCR between the two treatment regimens; however, in patients treated with an ICI, fatigue, rashes, diarrhea, and elevated aminotransferase enzymes were significantly increased (p < 0.05).

Conclusion

ICI combined with chemotherapy is superior to chemotherapy alone with respect to PFS and OS in patients with advanced SCLC.
Appendix
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Literature
go back to reference Antonia SJ, Mirza N, Fricke I (2006) Combination of p53 cancer vaccine with chemotherapy in patients with extensive stage small cell lung cancer. Clin Cancer Res 12(3 Pt 1):878–887CrossRef Antonia SJ, Mirza N, Fricke I (2006) Combination of p53 cancer vaccine with chemotherapy in patients with extensive stage small cell lung cancer. Clin Cancer Res 12(3 Pt 1):878–887CrossRef
go back to reference Braly P, Nicodemus CF, Chu C et al (2009) The immune adjuvant properties of front-line carboplatin-paclitaxel: a randomized phase 2 study of alternative schedules of intravenous oregovomab chemoimmunotherapy in advanced ovarian cancer. J Immunother 32(1):54–65CrossRef Braly P, Nicodemus CF, Chu C et al (2009) The immune adjuvant properties of front-line carboplatin-paclitaxel: a randomized phase 2 study of alternative schedules of intravenous oregovomab chemoimmunotherapy in advanced ovarian cancer. J Immunother 32(1):54–65CrossRef
go back to reference Bunn PJ, Minna JD, Augustyn A et al (2016) Small Cell lung cancer: can recent advances in biology and molecular biology be translated into improved outcomes? J Thorac Oncol 11(4):453–474CrossRef Bunn PJ, Minna JD, Augustyn A et al (2016) Small Cell lung cancer: can recent advances in biology and molecular biology be translated into improved outcomes? J Thorac Oncol 11(4):453–474CrossRef
go back to reference Chung HC, Lopez-Martin JA, Kao SC-H et al (2018) Phase 2 study of pembrolizumab in advanced small-cell lung cancer (SCLC): KeyNote-158. J Clin Oncol 36(15_suppl):8506CrossRef Chung HC, Lopez-Martin JA, Kao SC-H et al (2018) Phase 2 study of pembrolizumab in advanced small-cell lung cancer (SCLC): KeyNote-158. J Clin Oncol 36(15_suppl):8506CrossRef
go back to reference Curioni-Fontecedro A, Ickenberg C, Franzen D et al (2017) Diffuse pseudoprogression in a p-atient with metastatic non- small-cell lung cancer treated with Nivolumab. Ann Oncol 28(8):2040–2041CrossRef Curioni-Fontecedro A, Ickenberg C, Franzen D et al (2017) Diffuse pseudoprogression in a p-atient with metastatic non- small-cell lung cancer treated with Nivolumab. Ann Oncol 28(8):2040–2041CrossRef
go back to reference Gazdar AF, Bunn PA, Minna JD et al (2017) Small-cell lung cancer: what we know, what we need to know and the path forward. Nat Rev Cancer 17(12):725–737CrossRef Gazdar AF, Bunn PA, Minna JD et al (2017) Small-cell lung cancer: what we know, what we need to know and the path forward. Nat Rev Cancer 17(12):725–737CrossRef
go back to reference Govindan R, Ding L, Griffith M et al (2012) Genomic landscape of non-small cell lung cancer in smokers and never-smokers. Cell 150(6):1121–1134CrossRef Govindan R, Ding L, Griffith M et al (2012) Genomic landscape of non-small cell lung cancer in smokers and never-smokers. Cell 150(6):1121–1134CrossRef
go back to reference He Y, Rozeboom L, Rivard CJ et al (2017) MHC class II expression in lung cancer. Lung Cancer 112:75–80CrossRef He Y, Rozeboom L, Rivard CJ et al (2017) MHC class II expression in lung cancer. Lung Cancer 112:75–80CrossRef
go back to reference Hellmann MD, Callahan MK, Awad MM et al (2018) Tumor mutational burden and efficacy of nivolumab monotherapy and in combination with ipilimumab in small-cell lung cancer. Cancer Cell 33(5):853–861CrossRef Hellmann MD, Callahan MK, Awad MM et al (2018) Tumor mutational burden and efficacy of nivolumab monotherapy and in combination with ipilimumab in small-cell lung cancer. Cancer Cell 33(5):853–861CrossRef
go back to reference Hodi FS, O'Day SJ, McDermott DF et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723CrossRef Hodi FS, O'Day SJ, McDermott DF et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723CrossRef
go back to reference Horn L, Mansfield AS, Szczesna A et al (2018) First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med 379(23):2220–2229CrossRef Horn L, Mansfield AS, Szczesna A et al (2018) First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med 379(23):2220–2229CrossRef
go back to reference Kalemkerian GP, Schneider BJ (2017) Advances in small cell lung cancer. Hematol Oncol Clin North Am 31(1):143–156CrossRef Kalemkerian GP, Schneider BJ (2017) Advances in small cell lung cancer. Hematol Oncol Clin North Am 31(1):143–156CrossRef
go back to reference Kashima J, Okuma Y, Shimizuguchi R et al (2018) Bile duct obstruction in a patient treated with nivolumab as second-line chemotherapy for advanced non-small-cell lung cancer: a case report. Cancer Immunol Immunother 67(1):61–65CrossRef Kashima J, Okuma Y, Shimizuguchi R et al (2018) Bile duct obstruction in a patient treated with nivolumab as second-line chemotherapy for advanced non-small-cell lung cancer: a case report. Cancer Immunol Immunother 67(1):61–65CrossRef
go back to reference Korkolopoulou P, Kaklamanis L, Pezzella F et al (1996) Loss of antigen-presenting molecules (MHC class I and TAP-1) in lung cancer. Br J Cancer 73(2):148–153CrossRef Korkolopoulou P, Kaklamanis L, Pezzella F et al (1996) Loss of antigen-presenting molecules (MHC class I and TAP-1) in lung cancer. Br J Cancer 73(2):148–153CrossRef
go back to reference Krenacs T, Kiszner G, Stelkovics E et al (2012) Collagen XVII is expressed in malignant but not in benign melanocytic tumors and it can mediate antibody induced melanoma apoptosis. Histochem Cell Biol 138(4):653–667CrossRef Krenacs T, Kiszner G, Stelkovics E et al (2012) Collagen XVII is expressed in malignant but not in benign melanocytic tumors and it can mediate antibody induced melanoma apoptosis. Histochem Cell Biol 138(4):653–667CrossRef
go back to reference List M, Jamous F, Gupta A et al (2015) Anti-Hu positive antibodies and small cell carcinoma: a single center review. S D Med 68(6):253–255 List M, Jamous F, Gupta A et al (2015) Anti-Hu positive antibodies and small cell carcinoma: a single center review. S D Med 68(6):253–255
go back to reference Liu G, Chen T, Li R et al (2018) Well-controlled pleural effusion indicated pseudoprogression after immunotherapy in lung cancer: a case report. Thorac Cancer 9(9):1190–1193CrossRef Liu G, Chen T, Li R et al (2018) Well-controlled pleural effusion indicated pseudoprogression after immunotherapy in lung cancer: a case report. Thorac Cancer 9(9):1190–1193CrossRef
go back to reference Melian M, Lorente D, Aparici F et al (2018) Lung brain metastasis pseudoprogression after nivolumab and ipilimumab combination treatment. Thorac Cancer 9(12):1770–1773CrossRef Melian M, Lorente D, Aparici F et al (2018) Lung brain metastasis pseudoprogression after nivolumab and ipilimumab combination treatment. Thorac Cancer 9(12):1770–1773CrossRef
go back to reference Naidoo J, Page DB, Li BT et al (2015) Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol 26(12):2375–2391CrossRef Naidoo J, Page DB, Li BT et al (2015) Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol 26(12):2375–2391CrossRef
go back to reference Ott PA, Bang Y-J, Berton-Riguad D et al (2017) Safety and antitumor activity of pembrolizumab in advanced programmed death ligand-1-positive endometrial cancer: results from the K EY NOTE-028 study. J Clin Oncol 35(22):2535–2541CrossRef Ott PA, Bang Y-J, Berton-Riguad D et al (2017) Safety and antitumor activity of pembrolizumab in advanced programmed death ligand-1-positive endometrial cancer: results from the K EY NOTE-028 study. J Clin Oncol 35(22):2535–2541CrossRef
go back to reference Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12(4):252–264CrossRef Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12(4):252–264CrossRef
go back to reference Paz-Ares L, Dvorkin M, Chen Y et al (2019) 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 394(10212):1929–1939CrossRef Paz-Ares L, Dvorkin M, Chen Y et al (2019) 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 394(10212):1929–1939CrossRef
go back to reference Postow MA (2015) Managing immune checkpoint-blocking antibody side effects. Am Soc Clin Oncol Educ Book 35:76–83CrossRef Postow MA (2015) Managing immune checkpoint-blocking antibody side effects. Am Soc Clin Oncol Educ Book 35:76–83CrossRef
go back to reference Reck M, Bondarenko I, Luft A et al (2013) Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol 24(1):75–83CrossRef Reck M, Bondarenko I, Luft A et al (2013) Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol 24(1):75–83CrossRef
go back to reference Reck M, Luft A, Szczesna A et al (2016) Phase III randomized trial of ipilimumab plus etoposide and platinum versus placebo plus etoposide and platinum in extensive-stage small-cell lung cancer. J Clin Oncol 34(31):3740–3748CrossRef Reck M, Luft A, Szczesna A et al (2016) Phase III randomized trial of ipilimumab plus etoposide and platinum versus placebo plus etoposide and platinum in extensive-stage small-cell lung cancer. J Clin Oncol 34(31):3740–3748CrossRef
go back to reference Ricciuti B, Kravets S, Dahlberg SE et al (2019) Use of targeted next generation sequencing to characterize tumor mutational burden and efficacy of immune checkpoint inhibition in small cell lung cancer. J Immunother Cancer 7(1):87CrossRef Ricciuti B, Kravets S, Dahlberg SE et al (2019) Use of targeted next generation sequencing to characterize tumor mutational burden and efficacy of immune checkpoint inhibition in small cell lung cancer. J Immunother Cancer 7(1):87CrossRef
go back to reference Rocha P, Hardy-Werbin M, Naranjo D et al (2018) CD103+CD8+ lymphocytes characterize the immune infiltration in a case with pseudoprogression in squamous NSCLC. J Thorac Oncol 13(10):e193–e196CrossRef Rocha P, Hardy-Werbin M, Naranjo D et al (2018) CD103+CD8+ lymphocytes characterize the immune infiltration in a case with pseudoprogression in squamous NSCLC. J Thorac Oncol 13(10):e193–e196CrossRef
go back to reference Rudin CM, Awad MM, Navarro A et al (2020) Pembrolizumab or placebo plus etoposide and platinum as first-line therapy for extensive-stage small-cell lung cancer: randomized, double-blind, Phase III KEYNOTE-604 study. J Clin Oncol 38(21):2369–2379CrossRef Rudin CM, Awad MM, Navarro A et al (2020) Pembrolizumab or placebo plus etoposide and platinum as first-line therapy for extensive-stage small-cell lung cancer: randomized, double-blind, Phase III KEYNOTE-604 study. J Clin Oncol 38(21):2369–2379CrossRef
go back to reference Si X, Song P, Ni J et al (2020) Management of immune checkpoint inhibitor-related adverse events: a review of case reports. Thorac Cancer 11(3):498–504CrossRef Si X, Song P, Ni J et al (2020) Management of immune checkpoint inhibitor-related adverse events: a review of case reports. Thorac Cancer 11(3):498–504CrossRef
go back to reference Swami U, Smith M, Zhang J (2018) Central nervous system pseudoprogression with nivolumab in a patient with squamous cell lung cancer followed by prolonged response. J Thorac Oncol 13(9):e183–e184CrossRef Swami U, Smith M, Zhang J (2018) Central nervous system pseudoprogression with nivolumab in a patient with squamous cell lung cancer followed by prolonged response. J Thorac Oncol 13(9):e183–e184CrossRef
go back to reference Tazdait M, Mezquita L, Lahmar J et al (2018) Patterns of responses in metastatic NSCLC during PD-1 or PD-L1 inhibitor therapy: Comparison of RECIST 1.1, irRECIST and iRECIST criteria. Eur J Cancer 88:38–47CrossRef Tazdait M, Mezquita L, Lahmar J et al (2018) Patterns of responses in metastatic NSCLC during PD-1 or PD-L1 inhibitor therapy: Comparison of RECIST 1.1, irRECIST and iRECIST criteria. Eur J Cancer 88:38–47CrossRef
go back to reference Travis WD, Brambilla E, Burke A et al (2015) Introduction to the 2015 World Health Organization classification of tumors of the lung, pleura, thymus, and heart. J Thorac Oncol 10(9):1240–1242CrossRef Travis WD, Brambilla E, Burke A et al (2015) Introduction to the 2015 World Health Organization classification of tumors of the lung, pleura, thymus, and heart. J Thorac Oncol 10(9):1240–1242CrossRef
go back to reference Varghese AM, Zakowski MF, Yu HA et al (2014) Small-cell lung cancers in patients who never smoked cigarettes. J Thorac Oncol 9(6):892–896CrossRef Varghese AM, Zakowski MF, Yu HA et al (2014) Small-cell lung cancers in patients who never smoked cigarettes. J Thorac Oncol 9(6):892–896CrossRef
go back to reference Wang Q, Gao J, Wu X (2018) Pseudoprogression and hyperprogression after checkpoint blockade. Int Immunopharmacol 58:125–135CrossRef Wang Q, Gao J, Wu X (2018) Pseudoprogression and hyperprogression after checkpoint blockade. Int Immunopharmacol 58:125–135CrossRef
go back to reference Weber JS, Dummer R, de Pril V, Investigators MDX et al (2013) Patterns of onset and resolution of immune-related adverse events of special interest with ipilimumab: detailed safety analysis from a phase 3 trial in patients with advanced melanoma. Cancer 119:1675–1682CrossRef Weber JS, Dummer R, de Pril V, Investigators MDX et al (2013) Patterns of onset and resolution of immune-related adverse events of special interest with ipilimumab: detailed safety analysis from a phase 3 trial in patients with advanced melanoma. Cancer 119:1675–1682CrossRef
go back to reference Weber JS, Yang JC, Atkins MB et al (2015) Toxicities of immunotherapy for the practitioner. J Clin Oncol 33:2092–2099CrossRef Weber JS, Yang JC, Atkins MB et al (2015) Toxicities of immunotherapy for the practitioner. J Clin Oncol 33:2092–2099CrossRef
go back to reference Yamaura T, Suzuki H (2018) Pseudoprogression and rapid response to pembrolizumab in a patient with advanced lung adenocarcinoma with loss of epidermal growth factor receptor gene mutation after tyrosine kinase inhibitor therapy. J Thorac Oncol 13(10):e209–e210CrossRef Yamaura T, Suzuki H (2018) Pseudoprogression and rapid response to pembrolizumab in a patient with advanced lung adenocarcinoma with loss of epidermal growth factor receptor gene mutation after tyrosine kinase inhibitor therapy. J Thorac Oncol 13(10):e209–e210CrossRef
Metadata
Title
Efficacy and safety of immune checkpoint inhibitors (ICIs) in extensive-stage small cell lung cancer (SCLC)
Authors
Xiaoting Ma
Shan Wang
Yujian Zhang
Huamin Wei
Jing Yu
Publication date
01-02-2021
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 2/2021
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-020-03362-z

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