Incidence of skin adverse reactions in patients with lung cancer treated by immunotherapy: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

ZHANG Hui ¹ , WANG Sue ² , JI Shuo ² , XU Yan ² ,  PAN Ruili ²

1. School of Nursing, Peking Union Medical College, Beijing 100144, P.R.China;
2. Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Beijing 100730, P.R.China;

Corresponding author：

PAN Ruili, Email: dabaidexiapu0236@163.com

Keywords：

Lung cancer; Immunotherapy; Skin adverse reaction; Incidence; Meta-analysis; Systematic review

DOI：

10.7507/1672-2531.202109071

Video：

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Objective To systematically review the incidence of adverse skin reactions in lung cancer patients treated by immunotherapy. Methods PubMed, Web of Science, The Cochrane Library, CNKI, WanFang Data and VIP databases were electronically searched to collect the studies on the incidence of skin adverse reactions in lung cancer patients treated with immunotherapy from June 2011 to June 2021. Two reviewers independently screened literature, extracted data and assessed the risk bias of the included studies. Meta-analysis was then performed by using Stata 15.0 software. Results A total of 63 studies were included, with a total sample size of 13 386 cases. The results of meta-analysis showed that the overall incidence of adverse skin reactions in lung cancer patients was 14.0% (95%CI 11.6% to 16.5%). Conclusion Current evidence shows that the incidence of adverse skin reactions in lung cancer patients with immunotherapy is high. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusions.

Citation： ZHANG Hui, WANG Sue, JI Shuo, XU Yan, PAN Ruili. Incidence of skin adverse reactions in patients with lung cancer treated by immunotherapy: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2022, 22(1): 79-88. doi: 10.7507/1672-2531.202109071 Copy

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1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2. Cao W, Chen HD, Yu YW, et al. Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020. Chin Med J (Engl), 2021, 134(7): 783-791.
3. 陈丽君, 赵鹏, 曹科, 等. 免疫检查点抑制剂治疗非小细胞肺癌患者有效性及安全性的Meta分析. 肿瘤, 2018, 38(8): 780-791.
4. Santarpia M, Aguilar A, Chaib I, et al. Non-small-cell lung cancer signaling pathways, metabolism, and PD-1/PD-L1 antibodies. Cancers (Basel), 2020, 12(6): 1475.
5. Naidoo J, Page DB, Li BT, et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol, 2015, 26(12): 2375-2391.
6. Curry JL, Tetzlaff MT, Nagarajan P, et al. Diverse types of dermatologic toxicities from immune checkpoint blockade therapy. J Cutan Pathol, 2017, 44(2): 158-176.
7. 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.
8. Grangeon M, Tomasini P, Chaleat S, et al. Association between immune-related adverse events and efficacy of immune checkpoint inhibitors in non-small-cell lung cancer. Clin Lung Cancer, 2019, 20(3): 201-207.
9. Garrett NFMDS, da Costa ACC, Damiani G, et al. Patients with lung cancer undergoing immune checkpoint inhibitors: A meta-analysis of dermatological toxicities. Crit Rev Oncol Hematol, 2020, 152: 102983.
10. 曾宪涛, 刘慧, 陈曦, 等. Meta分析系列之四: 观察性研究的质量评价工具. 中国循证心血管医学杂志, 2012, 4(4): 297-299.
11. Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions (version 5.1. 0). The Cochrane Collaboration, 2011. Available at: http://www.cochrane-handbook.org.
12. 李柄辉, 訾豪, 李路遥, 等. 医学领域一次研究和二次研究的方法学质量(偏倚风险)评价工具. 医学新知, 2021, 31(1): 51-58.
13. Ricciuti B, Genova C, De Giglio A, et al. Impact of immune-related adverse events on survival in patients with advanced non-small cell lung cancer treated with nivolumab: long-term outcomes from a multi-institutional analysis. J Cancer Res Clin Oncol, 2019, 145(2): 479-485.
14. Amrane K, Geier M, Corre R, et al. First-line pembrolizumab for non-small cell lung cancer patients with PD-L1 ≥50% in a multicenter real-life cohort: The PEMBREIZH study. Cancer Med, 2020, 9(7): 2309-2316.
15. Cortellini A, Friedlaender A, Banna GL, et al. Immune-related adverse events of pembrolizumab in a large real-world cohort of patients with NSCLC with a PD-L1 expression ≥ 50% and their relationship with clinical outcomes. Clin Lung Cancer, 2020, 21(6): 498-508.
16. Mok TSK, Wu YL, Kudaba I, et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet, 2019, 393(10183): 1819-1830.
17. Ksienski D, Wai ES, Croteau N, et al. Pembrolizumab for advanced nonsmall cell lung cancer: Efficacy and safety in everyday clinical practice. Lung Cancer, 2019, 133: 110-116.
18. Muchnik E, Loh KP, Strawderman M, et al. Immune checkpoint inhibitors in real-world treatment of older adults with non-small cell lung cancer. J Am Geriatr Soc, 2019, 67(5): 905-912.
19. Krefting F, Basara N, Schütte W, et al. Clinical experience of immunotherapy treatment: efficacy and toxicity analysis of the compassionate use program of nivolumab in patients with advanced squamous cell non-small cell lung cancer. Oncol Res Treat, 2019, 42(5): 243-255.
20. Conde-Estévez D, Monge-Escartín I, Ríos-Hoyo A, et al. Prognostic factors and effect on survival of immune-related adverse events in patients with non-small-cell lung cancer treated with immune checkpoint blockage. J Chemother, 2021, 33(1): 32-39.
21. Gubens MA, Sequist LV, Stevenson JP, et al. Pembrolizumab in combination with ipilimumab as second-line or later therapy for advanced non-small-cell lung cancer: KEYNOTE-021 cohorts D and H. Lung Cancer, 2019, 130: 59-66.
22. Saito Z, Fujita K, Okamura M, et al. Efficacy and safety of immune checkpoint inhibitors in patients with non-small cell lung cancer aged 80 years or older. Cancer Rep (Hoboken), 2021: e1405.
23. Carbone DP, Reck M, Paz-Ares L, et al. First-line nivolumab in stage Ⅳ or recurrent non-small-cell lung cancer. N Engl J Med, 2017, 376(25): 2415-2426.
24. Hida T, Nishio M, Nogami N, et al. Efficacy and safety of nivolumab in Japanese patients with advanced or recurrent squamous non-small cell lung cancer. Cancer Sci, 2017, 108(5): 1000-1006.
25. Cortellini A, Chiari R, Ricciuti B, et al. Correlations between the immune-related adverse events spectrum and efficacy of Anti-PD1 immunotherapy in NSCLC patients. Clin Lung Cancer, 2019, 20(4): 237-247.
26. Hasan Ali O, Diem S, Markert E, et al. Characterization of nivolumab-associated skin reactions in patients with metastatic non-small cell lung cancer. Oncoimmunology, 2016, 5(11): e1231292.
27. Hellmann MD, Rizvi NA, Goldman JW, et al. Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): results of an open-label, phase 1, multicohort study. Lancet Oncol, 2017, 18(1): 31-41.
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Chinese Journal of Evidence-Based Medicine

Incidence of skin adverse reactions in patients with lung cancer treated by immunotherapy: a meta-analysis

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