Semin Respir Crit Care Med 2023; 44(04): 447-453
DOI: 10.1055/s-0043-1769092
Review Article

Malignant Pleural Effusions in the Era of Immunotherapy and Antiangiogenic Therapy

Terrence Wong
1   Department of Medicine, Geisel School of Medicine, Dartmouth, Hanover, New Hampshire
2   Division of Pulmonary and Critical Care Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
,
Alexander D. Fuld
3   Department of Medicine and Medical Education, Geisel School of Medicine, Dartmouth, Hanover, New Hampshire
4   Department of Medical Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
,
David J. Feller-Kopman
1   Department of Medicine, Geisel School of Medicine, Dartmouth, Hanover, New Hampshire
2   Division of Pulmonary and Critical Care Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
› Institutsangaben

Abstract

Malignant pleural effusions (MPE) have historically been associated with a poor prognosis, and patients often require a series of invasive procedures and hospitalizations that significantly reduce quality of life at the terminus of life. However, advances in the management of MPE have coincided with the era of immunotherapies, and to a lesser extent, antiangiogenic therapies for the treatment of lung cancer. Landmark studies have shown these drugs to improve overall survival and progression-free survival in patients with lung cancer, but a paucity of phase III trial data exists for the impact of immune checkpoint inhibitors (ICI) on lung cancers associated with MPE. This review will focus on the leading studies investigating the impact of ICI and antiangiogenic therapies in patients with lung cancer and MPE. The diagnostic and prognostic values of vascular endothelial growth factor and endostatin expression levels in malignancy will also be discussed. These advancements are changing the paradigm of MPE management from palliation to treatment for the first time since 1767 when MPE was first reported. The future holds the promise of durable response and extended survival in patients with MPE.



Publikationsverlauf

Artikel online veröffentlicht:
12. Juni 2023

© 2023. Thieme. All rights reserved.

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333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 Lieutaud J. Essais anatomiques, contenant l'histoire exacte de toutes les parties qui composent le corps de l'homme, avec la manière de disséquer, [Joseph Lieutaud]. Paris: 1742
  • 2 Robert C. A decade of immune-checkpoint inhibitors in cancer therapy. Nat Commun 2020; 11 (01) 3801
  • 3 He D, Ding R, Wen Q, Chen L. Novel therapies for malignant pleural effusion: Anti-angiogenic therapy and immunotherapy (review). Int J Oncol 2021; 58 (03) 359-370
  • 4 Gandhi L, Rodríguez-Abreu D, Gadgeel S. et al; KEYNOTE-189 Investigators. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med 2018; 378 (22) 2078-2092
  • 5 Borghaei H, Paz-Ares L, Horn L. et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 2015; 373 (17) 1627-1639
  • 6 Chen Y, Mathy NW, Lu H. The role of VEGF in the diagnosis and treatment of malignant pleural effusion in patients with non-small cell lung cancer (review). Mol Med Rep 2018; 17 (06) 8019-8030
  • 7 Porcel JM, Gasol A, Bielsa S, Civit C, Light RW, Salud A. Clinical features and survival of lung cancer patients with pleural effusions. Respirology 2015; 20 (04) 654-659
  • 8 Postmus PE, Brambilla E, Chansky K. et al; International Association for the Study of Lung Cancer International Staging Committee, Cancer Research and Biostatistics, Observers to the Committee, Participating Institutions. The IASLC Lung Cancer Staging Project: proposals for revision of the M descriptors in the forthcoming (seventh) edition of the TNM classification of lung cancer. J Thorac Oncol 2007; 2 (08) 686-693
  • 9 Akulian J, Feller-Kopman D. The past, current and future of diagnosis and management of pleural disease. J Thorac Dis 2015; 7 (uppl 4): S329-S338
  • 10 Clive AO, Kahan BC, Hooper CE. et al. Predicting survival in malignant pleural effusion: development and validation of the LENT prognostic score. Thorax 2014; 69 (12) 1098-1104
  • 11 Wahidi MM, Reddy C, Yarmus L. et al. Randomized trial of pleural fluid drainage frequency in patients with malignant pleural effusions. The ASAP trial. Am J Respir Crit Care Med 2017; 195 (08) 1050-1057
  • 12 Semaan R, Feller-Kopman D, Slatore C, Sockrider M. Malignant pleural effusions. Am J Respir Crit Care Med 2016; 194 (06) 11-12
  • 13 DeBiasi EM, Feller-Kopman D. Physiologic basis of symptoms in pleural disease. Semin Respir Crit Care Med 2019; 40 (03) 305-313
  • 14 Feller-Kopman D, Light R. Pleural disease. N Engl J Med 2018; 378 (08) 740-751
  • 15 Akulian J, Yarmus L, Feller-Kopman D. The evaluation and clinical application of pleural physiology. Clin Chest Med 2013; 34 (01) 11-19
  • 16 Feller-Kopman DJ, Reddy CB, DeCamp MM. et al. Management of malignant pleural effusions. An official ATS/STS/STR clinical practice guideline. Am J Respir Crit Care Med 2018; 198 (07) 839-849
  • 17 Bhatnagar R, Keenan EK, Morley AJ. et al. Outpatient talc administration by indwelling pleural catheter for malignant effusion. N Engl J Med 2018; 378 (14) 1313-1322
  • 18 Ost DE, Niu J, Zhao H, Grosu HB, Giordano SH. Quality gaps and comparative effectiveness of management strategies for recurrent malignant pleural effusions. Chest 2018; 153 (02) 438-452
  • 19 Psallidas I, Kanellakis NI, Gerry S. et al. Development and validation of response markers to predict survival and pleurodesis success in patients with malignant pleural effusion (PROMISE): a multicohort analysis. Lancet Oncol 2018; 19 (07) 930-939
  • 20 Shafiq M, Ma X, Taghizadeh N. et al. Healthcare costs and utilization among patients hospitalized for malignant pleural effusion. Respiration 2020; 99 (03) 257-263
  • 21 Shafiq M, Simkovich S, Hossen S, Feller-Kopman DJ. Indwelling pleural catheter drainage strategy for malignant effusion: a cost-effectiveness analysis. Ann Am Thorac Soc 2020; 17 (06) 746-753
  • 22 Shafiq M, Frick KD, Lee H, Yarmus L, Feller-Kopman DJ. Management of malignant pleural effusion: a cost-utility analysis. J Bronchol Interv Pulmonol 2015; 22 (03) 215-225
  • 23 Stathopoulos GT, Kalomenidis I. Malignant pleural effusion: tumor-host interactions unleashed. Am J Respir Crit Care Med 2012; 186 (06) 487-492
  • 24 Giannou AD, Marazioti A, Spella M. et al. Mast cells mediate malignant pleural effusion formation. J Clin Invest 2015; 125 (06) 2317-2334
  • 25 Murthy P, Ekeke CN, Russell KL. et al. Making cold malignant pleural effusions hot: driving novel immunotherapies. OncoImmunology 2019; 8 (04) e1554969
  • 26 Takeuchi E, Yanagawa H, Suzuki Y. et al. IL-12-induced production of IL-10 and interferon-gamma by mononuclear cells in lung cancer-associated malignant pleural effusions. Lung Cancer 2002; 35 (02) 171-177
  • 27 Donnenberg AD, Luketich JD, Dhupar R, Donnenberg VS. Treatment of malignant pleural effusions: the case for localized immunotherapy. J Immunother Cancer 2019; 7 (01) 110
  • 28 Chen YM, Yang WK, Whang-Peng J, Kuo BI, Perng RP. Elevation of interleukin-10 levels in malignant pleural effusion. Chest 1996; 110 (02) 433-436
  • 29 Thomas R, Cheah HM, Creaney J, Turlach BA, Lee YC. Longitudinal measurement of pleural fluid biochemistry and cytokines in malignant pleural effusions. Chest 2016; 149 (06) 1494-1500
  • 30 Heffner JE, Nietert PJ, Barbieri C. Pleural fluid pH as a predictor of pleurodesis failure: analysis of primary data. Chest 2000; 117 (01) 87-95
  • 31 Nie K, Zhang Z, You Y, Zhuang X, Zhang C, Ji Y. A randomized clinical study to compare intrapleural infusion with intravenous infusion of bevacizumab in the management of malignant pleural effusion in patients with non-small-cell lung cancer. Thorac Cancer 2020; 11 (01) 8-14
  • 32 Ma X, Yao Y, Yuan D. et al. Recombinant human endostatin Endostar suppresses angiogenesis and lymphangiogenesis of malignant pleural effusion in mice. PLoS One 2012; 7 (12) e53449
  • 33 Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 1989; 161 (02) 851-858
  • 34 Marquez-Medina D, Popat S. Closing faucets: the role of anti-angiogenic therapies in malignant pleural diseases. Clin Transl Oncol 2016; 18 (08) 760-768
  • 35 DeBiasi EM, Feller-Kopman D. Anatomy and applied physiology of the pleural space. Clin Chest Med 2021; 42 (04) 567-576
  • 36 Akulian J, Yarmus L, Feller-Kopman D. Tissue acquisition and specimen processing in the diagnosis of NSCLC. Semin Respir Crit Care Med 2013; 34 (06) 787-791
  • 37 Carter J, Miller JA, Feller-Kopman D, Ettinger D, Sidransky D, Maleki Z. Molecular profiling of malignant pleural effusion in metastatic non-small-cell lung carcinoma. the effect of preanalytical factors. Ann Am Thorac Soc 2017; 14 (07) 1169-1176
  • 38 Bradshaw M, Mansfield A, Peikert T. The role of vascular endothelial growth factor in the pathogenesis, diagnosis and treatment of malignant pleural effusion. Curr Oncol Rep 2013; 15 (03) 207-216
  • 39 Gkiozos I, Tsagouli S, Charpidou A. et al. Levels of vascular endothelial growth factor in serum and pleural fluid are independent predictors of survival in advanced non-small cell lung cancer: results of a prospective study. Anticancer Res 2015; 35 (02) 1129-1137
  • 40 Zhang Y, Yu LK, Lu GJ. et al. Prognostic values of VEGF and endostatin with malignant pleural effusions in patients with lung cancer. Asian Pac J Cancer Prev 2014; 15 (19) 8435-8440
  • 41 Fafliora E, Hatzoglou C, Gourgoulianis KI, Zarogiannis SG. Systematic review and meta-analysis of vascular endothelial growth factor as a biomarker for malignant pleural effusions. Physiol Rep 2016; 4 (24) e12978
  • 42 Chen Y, Liang B, Zhao YJ, Wang SC, Fan YB, Wu GP. Transcription expression and clinical significance of vascular endothelial growth factor mRNA and endostatin mRNA in pleural effusions of patients with lung cancer. Diagn Cytopathol 2012; 40 (04) 287-291
  • 43 Gu Y, Zhang M, Li GH. et al. Diagnostic values of vascular endothelial growth factor and epidermal growth factor receptor for benign and malignant hydrothorax. Chin Med J (Engl) 2015; 128 (03) 305-309
  • 44 Murthy V, Katzman D, Sterman DH. Intrapleural immunotherapy: an update on emerging treatment strategies for pleural malignancy. Clin Respir J 2019; 13 (05) 272-279
  • 45 Francisco LM, Salinas VH, Brown KE. et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med 2009; 206 (13) 3015-3029
  • 46 Prado-Garcia H, Romero-Garcia S, Puerto-Aquino A, Rumbo-Nava U. The PD-L1/PD-1 pathway promotes dysfunction, but not “exhaustion”, in tumor-responding T cells from pleural effusions in lung cancer patients. Cancer Immunol Immunother 2017; 66 (06) 765-776
  • 47 Shiravand Y, Khodadadi F, Kashani SMA. et al. Immune checkpoint inhibitors in cancer therapy. Curr Oncol 2022; 29 (05) 3044-3060
  • 48 Johnson DB, Nebhan CA, Moslehi JJ, Balko JM. Immune-checkpoint inhibitors: long-term implications of toxicity. Nat Rev Clin Oncol 2022; 19 (04) 254-267
  • 49 Callahan MK, Wolchok JD. At the bedside: CTLA-4- and PD-1-blocking antibodies in cancer immunotherapy. J Leukoc Biol 2013; 94 (01) 41-53
  • 50 Grosu HB, Arriola A, Stewart J. et al. PD-L1 detection in histology specimens and matched pleural fluid cell blocks of patients with NSCLC. Respirology 2019; 24 (12) 1198-1203
  • 51 Lee PH, Yang TY, Chen KC. et al. Higher CD4/CD8 ratio of pleural effusion predicts better survival for lung cancer patients receiving immune checkpoint inhibitors. Sci Rep 2021; 11 (01) 9381
  • 52 Tamiya M, Tamiya A, Inoue T. et al. Metastatic site as a predictor of nivolumab efficacy in patients with advanced non-small cell lung cancer: a retrospective multicenter trial. PLoS One 2018; 13 (02) e0192227
  • 53 Shibaki R, Murakami S, Shinno Y. et al. Malignant pleural effusion as a predictor of the efficacy of anti-PD-1 antibody in patients with non-small cell lung cancer. Thorac Cancer 2019; 10 (04) 815-822
  • 54 Kawachi H, Tamiya M, Tamiya A. et al. Association between metastatic sites and first-line pembrolizumab treatment outcome for advanced non-small cell lung cancer with high PD-L1 expression: a retrospective multicenter cohort study. Invest New Drugs 2020; 38 (01) 211-218
  • 55 Morita M, Tamiya M, Fujimoto D. et al. Prediction of patients with a tumor proportion score > 50% who do not respond to first-line monotherapy with pembrolizumab. BMC Cancer 2020; 20 (01) 93
  • 56 Kawachi H, Tamiya M, Taniguchi Y. et al. Efficacy of immune checkpoint inhibitor with or without chemotherapy for nonsquamous NSCLC with malignant pleural effusion: a retrospective multicenter cohort study. JTO Clin Res Rep 2022; 3 (07) 100355
  • 57 Liu Y, Wang L, Song Q. et al. Intrapleural nano-immunotherapy promotes innate and adaptive immune responses to enhance anti-PD-L1 therapy for malignant pleural effusion. Nat Nanotechnol 2022; 17 (02) 206-216
  • 58 Chellappan DK, Leng KH, Jia LJ. et al. The role of bevacizumab on tumour angiogenesis and in the management of gynaecological cancers: a review. Biomed Pharmacother 2018; 102: 1127-1144
  • 59 Tamiya M, Tamiya A, Yamadori T. et al. Phase2 study of bevacizumab with carboplatin-paclitaxel for non-small cell lung cancer with malignant pleural effusion. Med Oncol 2013; 30 (03) 676
  • 60 Du N, Li X, Li F. et al. Intrapleural combination therapy with bevacizumab and cisplatin for non-small cell lung cancer-mediated malignant pleural effusion. Oncol Rep 2013; 29 (06) 2332-2340
  • 61 Usui K, Sugawara S, Nishitsuji M. et al; North East Japan Study Group. A phase II study of bevacizumab with carboplatin-pemetrexed in non-squamous non-small cell lung carcinoma patients with malignant pleural effusions: North East Japan Study Group Trial NEJ013A. Lung Cancer 2016; 99: 131-136
  • 62 Eisenhauer EA, Therasse P, Bogaerts J. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45 (02) 228-247
  • 63 Shen B, Tan M, Wang Z. et al. The meta-analysis of bevacizumab combined with platinum-based treatment of malignant pleural effusions by thoracic perfusion. J Oncol 2022; 2022: 1476038
  • 64 Ishii H, Yazawa T, Sato H. et al. Enhancement of pleural dissemination and lymph node metastasis of intrathoracic lung cancer cells by vascular endothelial growth factors (VEGFs). Lung Cancer 2004; 45 (03) 325-337
  • 65 Prager GW, Lackner EM, Krauth MT. et al. Targeting of VEGF-dependent transendothelial migration of cancer cells by bevacizumab. Mol Oncol 2010; 4 (02) 150-160
  • 66 Wang J, Sun Y, Liu Y. et al. [Results of randomized, multicenter, double-blind phase III trial of rh-endostatin (YH-16) in treatment of advanced non-small cell lung cancer patients]. Zhongguo Fei Ai Za Zhi 2005; 8 (04) 283-290
  • 67 Zhao WY, Chen DY, Chen JH, Ji ZN. Effects of intracavitary administration of Endostar combined with cisplatin in malignant pleural effusion and ascites. Cell Biochem Biophys 2014; 70 (01) 623-628
  • 68 Wang Z, Zheng Y, Fang Z. The clinical efficacy and safety of paclitaxel combined with Avastin for NSCLC patients diagnosed with malignant pleural effusion. Rev Assoc Med Bras (1992) 2018; 64 (03) 230-233
  • 69 Huang R, Zhan Q, Zhou X, Chu Z, Jiang J, Liang X. Continuous administration of recombinant human endostatin (Endostar): a pre-clinical safety study. Exp Ther Med 2012; 3 (06) 1018-1022
  • 70 Xia Y, Fang P, Zhang X, Su G, Shen A. The efficacy of Endostar combined with platinum pleural infusion for malignant pleural effusion in tumor patients is significantly better than that of monotherapy, but the economy is lower: a systematic review, network meta-analysis and cost-effectiveness analysis. Ann Transl Med 2022; 10 (10) 604
  • 71 Jie Wang X, Miao K, Luo Y. et al. Randomized controlled trial of Endostar combined with cisplatin/pemetrexed chemotherapy for elderly patients with advanced malignant pleural effusion of lung adenocarcinoma. J BUON 2018; 23 (01) 92-97