Clinical efficacy of paclitaxel and carboplatin with versus without bevacizumab in treatment of advanced non-small cell lung cancer: A systematic review and meta-analysis_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

LUO Xiaotong ^1,2 ,  DONG Xinchun ² ,  GOU Yunjiu ² , JIN Dacheng ² , ZHANG Siyuan ^1,2 , HUANG Daxin ^1,2

1. First Department of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou, 730000, P. R. China;
2. Department of Thoracic Surgery, The Gansu Provincial Hospital, Lanzhou, 730000, P. R. China;

Corresponding author：

DONG Xinchun, Email: 3050319523@qq.com; GOU Yunjiu, Email: gouyunjiu@163.com

Keywords：

Bevacizumab; paclitaxel; carboplatin; non-small cell lung cancer; systematic review/meta-analysis

DOI：

10.7507/1007-4848.202101014

Video：

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Objective To systematically evaluate the clinical efficacy and adverse reactions of paclitaxel and carboplatin with or without bevacizumab in the treatment of non-small cell lung cancer (NSCLC).Methods The databases including PubMed, The Cochrane Library, EMbase, CNKI, Wanfang Data, VIP and CBM were searched from inception to October 2022 to collect randomized controlled trials of the clinical efficacy of paclitaxel and carboplatin with or without bevacizumab for the treatment of NSCLC. RevMan 5.4 software was used for meta-analysis.Results Eight randomized controlled trials were enrolled, involving a total of 1 724 patients. Meta-analysis showed that for the treatment of NSCLC, the disease control rate, overall response rate, 1-year survival rate, and 2-year survival rate were higher in the trial group (paclitaxel and carboplatin combined with bevacizumab) than those in the control group (paclitaxel and carboplatin) (P<0.05); however, the incidences of the adverse reactions, such as leukopenia, hemorrhage, proteinuria and hypertension, etc, were higher in the trial group than those in the control group (P<0.05). There were no statistical differences between the trial group and the control group in the incidences of fatigue, thrombocytopenia, neutropenia or hyponatremia, etc (P>0.05). In addition, the median progression-free survival and overall survival were longer in the trial group than those in the control group.Conclusion For the treatment of NSCLC, paclitaxel and carboplatin combined with bevacizumab is superior in terms of disease control, overall response and prolonging patient survival, etc, but will be associated with more adverse reactions.

Citation： LUO Xiaotong, DONG Xinchun, GOU Yunjiu, JIN Dacheng, ZHANG Siyuan, HUANG Daxin. Clinical efficacy of paclitaxel and carboplatin with versus without bevacizumab in treatment of advanced non-small cell lung cancer: A systematic review and meta-analysis. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2023, 30(1): 126-132. doi: 10.7507/1007-4848.202101014 Copy

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15.	Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med, 2004, 350(23): 2335-2342.
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24.	Ding T, Li ZT, Zhang X, et al. Comparison of carboplatin and paclitaxel with or without bevacizumab in chemotherapeutic regimens for unresectable stage Ⅲ non-small cell lung cancer. Eur Rev Med Pharmacol Sci, 2017, 21(16): 3723-3729.
25.	Soria JC, Márk Z, Zatloukal P, et al. Randomized phase Ⅱ study of dulanermin in combination with paclitaxel, carboplatin, and bevacizumab in advanced non-small-cell lung cancer. J Clin Oncol, 2011, 29: 4442-4451.
26.	宋琳, 韩芸, 魏丽群, 等. 贝伐珠单抗联合紫杉醇/卡铂方案对晚期非鳞非小细胞肺癌患者相关细胞生长因子及肿瘤标志物的影响. 实用药物与临床, 2020, 23(6): 510-513.
27.	贵永贤. 贝伐单抗联合紫杉醇+卡铂治疗晚期非小细胞肺癌的效果. 中国卫生工程学, 2019, 18(2): 299-301.
28.	Lewis SJ, Zammit S, Gunnell D, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ Clinical Research, 1997, 315(1): 629-634.
29.	Garcia J, Hurwitz HI, Sandler AB, et al. Bevacizumab (Avastin^®) in cancer treatment: A review of 15 years of clinical experience and future outlook. Cancer Treat Rev, 2020, 86: 102017.
30.	Ferrara N, Hillan KJ, Gerber HP, et al. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov, 2004, 3(5): 391-400.
31.	Ferrara N, Adamis AP. Ten years of anti-vascular endothelial growth factor therapy. Nat Rev Drug Discov, 2016, 15(6): 385-403.
32.	Al-Abd AM, Alamoudi AJ, Abdel-Naim AB, et al. Anti-angiogenic agents for the treatment of solid tumors: Potential pathways, therapy and current strategies—A review. J Adv Res, 2017, 8(6): 591-605.
33.	Rajabi M, Mousa SA. The role of angiogenesis in cancer treatment. Biomedicines, 2017, 5(2): 34.
34.	Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med, 2002, 346(2): 92-98.
35.	Socinski MA, Jotte RM, Cappuzzo F, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med, 2018, 378(24): 2288-2301.
36.	Reinmuth N, Bryl M, Bondarenko I, et al. PF-06439535 (a bevacizumab biosimilar) compared with reference bevacizumab (Avastin®), both plus paclitaxel and carboplatin, as first-line treatment for advanced non-squamous non-small-cell lung cancer: A randomized, double-blind study. BioDrugs, 2019, 33(5): 555-570.

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin, 2016, 66(1): 7-30.
2. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
3. Gridelli C, Maione P, Rossi A, et al. Treatment of advanced non-small-cell lung cancer in the elderly. Lung Cancer, 2009, 66(3): 282-286.
4. 温珍平, 韩雅玲. 晚期非小细胞肺癌维持治疗进展. 国际肿瘤学杂志, 2016, 43(2): 148-151.
5. 李艳, 郭其森. 晚期非小细胞肺癌维持治疗进展. 中华肿瘤防治杂志, 2014, 21(10): 800-804.
6. Azzoli CG, Baker S, Temin S, et al. American Society of Clinical Oncology clinical practice guideline update on chemotherapy for stage Ⅳ non-small-cell lung cancer. J Clin Oncol, 2009, 27(36): 6251-6266.
7. 王新, 姜达. 晚期非小细胞肺癌化疗联合免疫治疗进展. 中国肿瘤临床, 2018, 45(24): 55-60.
8. 赵静, 张晓彤, 胡克, 等. 紫杉醇联合卡铂三周方案同步胸部放疗治疗不宜手术的局部晚期非小细胞肺癌疗效和安全性研究: 一项来自单中心的回顾性研究. 中国肺癌杂志, 2016, 19(11): 731-737.
9. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell, 2000, 100(1): 57-70.
10. Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst, 1990, 82(1): 4-6.
11. Ferrara N. The role of vascular endothelial growth factor in pathological angiogenesis. Breast Cancer Res Treat, 1995, 36(2): 127-137.
12. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med, 2003, 9(6): 669-676.
13. Hegde PS, Wallin JJ, Mancao C. Predictive markers of anti-VEGF and emerging role of angiogenesis inhibitors as immunotherapeutics. Semin Cancer Biol, 2018, 52(Pt 2): 117-124.
14. Chen DS, Hurwitz H. Combinations of bevacizumab with cancer immunotherapy. Cancer J, 2018, 24(4): 193-204.
15. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med, 2004, 350(23): 2335-2342.
16. Tewari KS, Sill MW, Long HJ, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med, 2014, 370(8): 734-743.
17. Greenland S. Invited commentary: A critical look at some popular meta-analytic methods. Am J Epidemiol, 1994, 140(3): 290-296.
18. Petitti DB. Meta-Analysis, Decision Analysis, and Cost-Effectiveness Analysis: Methods for Quantitative Synthesis in Medicine. New York: Oxford University Press, 2002.
19. Thompson SG. Meta-analysis of clinical trials. Biostatistics decoded. Armitage P, Colton T, eds. Encyclopedia of Biostatistics. New York: Wiley-Blackwell, 2005.
20. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med, 2006, 355(24): 2542-2550.
21. Zhou C, Wu YL, Chen G, et al. BEYOND: A randomized, double-blind, placebo-controlled, multicenter, phase Ⅲ study of first-line carboplatin/paclitaxel plus bevacizumab or placebo in Chinese patients with advanced or recurrent nonsquamous non-small-cell lung cancer. J Clin Oncol, 2015, 33(19): 2197-2204.
22. Johnson DH, Fehrenbacher L, Novotny WF, et al. Randomized phase Ⅱ trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol, 2004, 22(11): 2184-2191.
23. Niho S, Kunitoh H, Nokihara H, et al. Randomized phase Ⅱ study of first-line carboplatin-paclitaxel with or without bevacizumab in Japanese patients with advanced non-squamous non-small-cell lung cancer. Lung Cancer, 2012, 76(3): 362-367.
24. Ding T, Li ZT, Zhang X, et al. Comparison of carboplatin and paclitaxel with or without bevacizumab in chemotherapeutic regimens for unresectable stage Ⅲ non-small cell lung cancer. Eur Rev Med Pharmacol Sci, 2017, 21(16): 3723-3729.
25. Soria JC, Márk Z, Zatloukal P, et al. Randomized phase Ⅱ study of dulanermin in combination with paclitaxel, carboplatin, and bevacizumab in advanced non-small-cell lung cancer. J Clin Oncol, 2011, 29: 4442-4451.
26. 宋琳, 韩芸, 魏丽群, 等. 贝伐珠单抗联合紫杉醇/卡铂方案对晚期非鳞非小细胞肺癌患者相关细胞生长因子及肿瘤标志物的影响. 实用药物与临床, 2020, 23(6): 510-513.
27. 贵永贤. 贝伐单抗联合紫杉醇+卡铂治疗晚期非小细胞肺癌的效果. 中国卫生工程学, 2019, 18(2): 299-301.
28. Lewis SJ, Zammit S, Gunnell D, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ Clinical Research, 1997, 315(1): 629-634.
29. Garcia J, Hurwitz HI, Sandler AB, et al. Bevacizumab (Avastin^®) in cancer treatment: A review of 15 years of clinical experience and future outlook. Cancer Treat Rev, 2020, 86: 102017.
30. Ferrara N, Hillan KJ, Gerber HP, et al. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov, 2004, 3(5): 391-400.
31. Ferrara N, Adamis AP. Ten years of anti-vascular endothelial growth factor therapy. Nat Rev Drug Discov, 2016, 15(6): 385-403.
32. Al-Abd AM, Alamoudi AJ, Abdel-Naim AB, et al. Anti-angiogenic agents for the treatment of solid tumors: Potential pathways, therapy and current strategies—A review. J Adv Res, 2017, 8(6): 591-605.
33. Rajabi M, Mousa SA. The role of angiogenesis in cancer treatment. Biomedicines, 2017, 5(2): 34.
34. Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med, 2002, 346(2): 92-98.
35. Socinski MA, Jotte RM, Cappuzzo F, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med, 2018, 378(24): 2288-2301.
36. Reinmuth N, Bryl M, Bondarenko I, et al. PF-06439535 (a bevacizumab biosimilar) compared with reference bevacizumab (Avastin®), both plus paclitaxel and carboplatin, as first-line treatment for advanced non-squamous non-small-cell lung cancer: A randomized, double-blind study. BioDrugs, 2019, 33(5): 555-570.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Clinical efficacy of paclitaxel and carboplatin with versus without bevacizumab in treatment of advanced non-small cell lung cancer: A systematic review and meta-analysis

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