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Cancer Innovation 2022, 1(2): 183-193 https://doi.org/10.1002/cai2.23
Review | Open Access | Issue | Published: 08 August 2022

Opportunities and challenges of immune checkpoint inhibitors for extensive‐stage small‐cell lung cancer

Show Author's Information Jing Zhao1,2,  Xiaoli Zhuo1,2,  Lei Liu1,2,  Zhe Yang1,3( ),  Guobin Fu1,3 ( )
The Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
The Department of Oncology, The College of Clinical Medicine, Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan, China
The Department of Oncology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
Keywords:
targeted therapy, small‐cell lung cancer, immune checkpoint inhibitors, molecular typing
Cite this article:
Zhao J, Zhuo X, Liu L, et al. Opportunities and challenges of immune checkpoint inhibitors for extensive‐stage small‐cell lung cancer. Cancer Innovation, 2022, 1(2): 183-193. https://doi.org/10.1002/cai2.23
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Abstract Full text About this article

Small‐cell lung cancer (SCLC) accounts for 15%–20% of primary lung cancers, and it is characterized by low differentiation, rapid proliferation, and early metastasis. At least two‐thirds of SCLC patients present with the extensive stage (ES) at the time of initial clinical diagnosis. Over the last 2 decades, platinum‐based combination chemotherapy has remained the standard first‐line treatment for SCLC. With the introduction of the immunotherapy era, immunotherapy plus chemotherapy has replaced conventional chemotherapy as the first‐line treatment option for ES‐SCLC and is recommended by National Comprehensive Cancer Network clinical guidelines. Therefore, in this review, we present the latest research advances in SCLC treatment, predictive biomarkers, and other topics of high interest to provide options for patients with SCLC.


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Opportunities and challenges of immune checkpoint inhibitors for extensive‐stage small‐cell lung cancer

Show Author's information Jing Zhao1,2, Xiaoli Zhuo1,2, Lei Liu1,2, Zhe Yang1,3( ), Guobin Fu1,3 ( )
The Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
The Department of Oncology, The College of Clinical Medicine, Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan, China
The Department of Oncology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China

Abstract

Small‐cell lung cancer (SCLC) accounts for 15%–20% of primary lung cancers, and it is characterized by low differentiation, rapid proliferation, and early metastasis. At least two‐thirds of SCLC patients present with the extensive stage (ES) at the time of initial clinical diagnosis. Over the last 2 decades, platinum‐based combination chemotherapy has remained the standard first‐line treatment for SCLC. With the introduction of the immunotherapy era, immunotherapy plus chemotherapy has replaced conventional chemotherapy as the first‐line treatment option for ES‐SCLC and is recommended by National Comprehensive Cancer Network clinical guidelines. Therefore, in this review, we present the latest research advances in SCLC treatment, predictive biomarkers, and other topics of high interest to provide options for patients with SCLC.

Keywords: targeted therapy, small‐cell lung cancer, immune checkpoint inhibitors, molecular typing

References(41)

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–32.
DOI Google Scholar
Torre LA, Siegel RL, Jemal A. Lung cancer statistics. Adv Exp Med Biol. 2016;893:1–19.
DOI Google Scholar
Byers LA, Rudin CM. Small cell lung cancer: where do we go from here?Cancer. 2015;121(5):664–72.
DOI Google Scholar
Ganti AKP, Loo BW, Bassetti M, Blakely C, Chiang A, D'Amico TA, et al. Small cell lung cancer, version 2.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2021;19(12):1441–64.
DOI Google Scholar
Kalemkerian GP, Schneider BJ. Advances in small cell lung cancer. Hematol Oncol Clin North Am. 2017;31(1):143–56.
DOI Google Scholar
Steven A, Fisher SA, Robinson BW. Immunotherapy for lung cancer. Respirology. 2016;21(5):821–33.
DOI Google Scholar
Ready NE, Ott PA, Hellmann MD, Zugazagoitia J, Hann CL, de Braud F, et al. Nivolumab monotherapy and nivolumab plus ipilimumab in recurrent small cell lung cancer: results from the Checkmate 032 randomized cohort. J Thorac Oncol. 2020;15(3):426–35.
DOI Google Scholar
Keeping ST, Cope S, Chan K, Wilson FR, Jansen JP, Penrod JR, et al. Comparative effectiveness of nivolumab versus standard of care for third‐line patients with small‐cell lung cancer. J Comp Eff Res. 2020;9(18):1275–84.
DOI Google Scholar
Spigel DR, Vicente D, Ciuleanu TE, Gettinger S, Peters S, Horn L, et al. Second‐line nivolumab in relapsed small‐cell lung cancer: Checkmate 331☆. Ann Oncol. 2021;32(5):631–41.
DOI Google Scholar
Warner AB, Postow MA. Bigger is not always better: tumor size and prognosis in advanced melanoma. Clin Cancer Res. 2018;24(20):4915–17.
DOI Google Scholar
Botticelli A, Salati M, Di Pietro FR, Strigari L, Cerbelli B, Zizzari IG, et al. A nomogram to predict survival in non‐small cell lung cancer patients treated with nivolumab. J Transl Med. 2019;17(1):99.
DOI Google Scholar
Hermes A, Gatzemeier U, Waschki B, Reck M. Lactate dehydrogenase as prognostic factor in limited and extensive disease stage small cell lung cancer—a retrospective single institution analysis. Respir Med. 2010;104(12):1937–42.
DOI Google Scholar
Nakazawa K, Kurishima K, Tamura T, Kagohashi K, Ishikawa H, Satoh H, et al. Specific organ metastases and survival in small cell lung cancer. Oncol Lett. 2012;4(4):617–20.
DOI Google Scholar
Chung HC, Piha‐Paul SA, Lopez‐Martin J, Schellens J, Kao S, Miller WH Jr, 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):618–27.
DOI Google Scholar
Owonikoko TK, Park K, Govindan R, Ready N, Reck M, Peter S, et al. Nivolumab and ipilimumab as maintenance therapy in extensive‐disease small‐cell lung cancer: checkmate 451. J Clin Oncol. 2021;39(12):1349–59.
DOI Google Scholar
Rabinovich GA, Gabrilovich D, Sotomayor EM. Immunosuppressive strategies that are mediated by tumor cells. Annu Rev Immunol. 2007;25:267–96.
DOI Google Scholar
Russ AJ, Wentworth L, Xu K, Rakhmilevich A, Seroogy CM, Sondel PM, et al. Suppression of T‐cell expansion by melanoma is exerted on resting cells. Ann Surg Oncol. 2011;18(13):3848–57.
DOI Google Scholar
Welters MJ, van der Sluis TC, van Meir H, Loof NM, van Ham VJ, van Duikeren S, et al. Vaccination during myeloid cell depletion by cancer chemotherapy fosters robust T cell responses. Sci Transl Med. 2016;8(334):334ra352.
DOI Google Scholar
Melief CJM, Welters MJP, Vergote I, Kroep JR, Kenter GG, Ottevanger PB, et al. Strong vaccine responses during chemotherapy are associated with prolonged cancer survival. Sci Transl Med. 2020;12(535):eaaz8235.
DOI Google Scholar
Salas‐Benito D, Pérez‐Gracia JL, Ponz‐Sarvisé M, Rodriguez‐Ruiz ME, Martínez‐Forero I, Castañón E, et al. Paradigms on immunotherapy combinations with chemotherapy. Cancer Discov. 2021;11(6):1353–67.
DOI Google Scholar
Reck M, Luft A, Szczesna A, Havel L, Kim S‐W, Akerley W, et al. 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. 2016;34(31):3740–48.
DOI Google Scholar
Blair HA. Atezolizumab: a review in previously treated advanced non‐small cell lung cancer. Target Oncol. 2018;13(3):399–407.
DOI Google Scholar
Ishii H, Azuma K, Kawahara A, Kinoshita T, Kage M, Hoshino T, et al. Significance of programmed cell death‐ligand 1 expression and its association with survival in patients with small cell lung cancer. J Thorac Oncol. 2015;10(3):426–30.
DOI Google Scholar
Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, et al. Updated overall survival and pd‐l1 subgroup analysis of patients with extensive‐stage small‐cell lung cancer treated with atezolizumab, carboplatin, and etoposide (impower133). J Clin Oncol. 2021;39(6):619–30.
DOI Google Scholar
Paz‐Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, 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):1929–39.
DOI Google Scholar
Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, et al. Durvalumab, with or without tremelimumab, plus platinum‐etoposide versus platinum‐etoposide alone in first‐line treatment of extensive‐stage small‐cell lung cancer (CASPIAN): updated results from a randomised, controlled, open‐label, phase 3 trial. Lancet Oncol. 2021;22(1):51–65.
DOI Google Scholar
Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Durvalumab after chemoradiotherapy in stage III non‐small‐cell lung cancer. N Engl J Med. 2017;377(20):1919–29.
DOI Google Scholar
Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, et al. 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. 2020;38(21):2369–79.
DOI Google Scholar
Giaj Levra M, Cotté FE, Corre R, Calvet C, Gaudin AF, Penrod JR, et al. Immunotherapy rechallenge after nivolumab treatment in advanced non‐small cell lung cancer in the real‐world setting: a national data base analysis. Lung Cancer. 2020;140:99–106.
DOI Google Scholar
Lupo G, Caporarello N, Olivieri M, Cristaldi M, Motta C, Bramanti V, et al. Anti‐angiogenic therapy in cancer: downsides and new pivots for precision medicine. Front Pharmacol. 2016;7:519.
DOI Google Scholar
Huang Y, Kim BYS, Chan CK, Hahn SM, Weissman IL, Jiang W. Improving immune‐vascular crosstalk for cancer immunotherapy. Nat Rev Immunol. 2018;18(3):195–203.
DOI Google Scholar
Fan Y, Zhao J, Wang Q, Huang D, Li X, Chen J, et al. Camrelizumab plus apatinib in extensive‐stage SCLC (PASSION): a multicenter, two‐stage, phase 2 trial. J Thorac Oncol. 2021;16(2):299–309.
DOI Google Scholar
Giffin MJ, Cooke K, Lobenhofer EK, Estrada J, Zhan J, Deegen P, et al. AMG 757, a half‐life extended, DLL3‐targeted bispecific t‐cell engager, shows high potency and sensitivity in preclinical models of small‐cell lung cancer. Clin Cancer Res. 2021;27(5):1526–37.
DOI Google Scholar
Blackhall F, Jao K, Greillier L, Cho BC, Penkov K, Reguart N, et al. Efficacy and safety of rovalpituzumab tesirine compared with topotecan as second‐line therapy in DLL3‐high SCLC: results from the phase 3 TAHOE study. J Thorac Oncol.2021;16(9):1547–58.
DOI Google Scholar
Taromi S, Firat E, Simonis A, Braun LM, Apostolova P, Elze M, et al. Enhanced AC133‐specific Car T cell therapy induces durable remissions in mice with metastatic small cell lung cancer. Cancer Lett. 2021;520:385–99.
DOI Google Scholar
Chen X, Amar N, Zhu Y, Wang C, Xia C, Yang X, et al. Combined DLL3‐targeted bispecific antibody with pd‐1 inhibition is efficient to suppress small cell lung cancer growth. J Immunother Cancer. 2020;8(1):e000785.
DOI Google Scholar
Sun C, Zhang L, Zhang W, Liu Y, Chen B, Zhao S, et al. Expression of PD‐1 and PD‐L1 on tumor‐infiltrating lymphocytes predicts prognosis in patients with small‐cell lung cancer. Onco Targets Ther. 2020;13:6475–83.
DOI Google Scholar
Rudin CM, Poirier JT, Byers LA, Dive C, Dowlati A, George J, et al. Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data. Nat Rev Cancer. 2019;19(5):289–97.
DOI Google Scholar
Gay CM, Stewart CA, Park EM, Diao L, Groves SM, Heeke S, et al. Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities. Cancer Cell. 2021;39(3):346–60.
DOI Google Scholar
Skoulidis F, Byers LA, Diao L, Papadimitrakopoulou VA, Tong P, Izzo J, et al. Co‐occurring genomic alterations define major subsets of KRAS‐mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities. Cancer Discovery. 2015;5(8):860–77.
DOI Google Scholar
Wang Z, Zhao J, Ma Z, Cui J, Shu Y, Liu Z, et al. A phase 2 study of tislelizumab in combination with platinum‐based chemotherapy as first‐line treatment for advanced lung cancer in Chinese patients. Lung Cancer. 2020;147:259–68.
DOI Google Scholar
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Publication history

Received: 29 April 2022
Revised: 29 May 2022
Accepted: 29 June 2022
Published: 08 August 2022
Issue date: August 2022

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© 2022 The Authors.

Acknowledgements

We sincerely thank Jingjiang Lai, Fengxian Jiang, Jingliang Wang, and Wei Xu for their help in data collection and manuscript editing.

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This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

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