晚期非小细胞肺癌抗血管生成药物治疗中国专家共识(2019版)
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摘要
<正>1引言肺癌是目前全球最常见和致死率最高的恶性肿瘤。2018年全球肺癌新发病例高达209万余例,肺癌造成的死亡人数高达176万余例~([1])。肺癌是我国男性最常见的癌症,2018年我国约有77.4万的新增肺癌病例,约有69万人死于肺癌~([2])。非小细胞肺癌(non-small cell lung cancer, NSCLC)是肺癌中最常见的组织学类型,在肺癌病例中占比超过
引文
1 GLOBOCAN 2018(IARC),Available at:http://gco.iarc.fr/.
2 http://gco.iarc.fr/today/data/factsheets/populations/160-china-factsheets.pdf.
3 Cufer T,Knez L.Update on systemic therapy of advanced non-smallcell lung cancer.Expert Rev Anticancer Ther,2014,14(10):1189-1203.doi:10.1586/14737140.2014.940327
4 Han BH.Epidemiology of lung cancer by molecular subtype in China.Presented by Baohui Han,16th WCLC,2015.
5 Gettinger S,Horn L,Jackman D,et al.Five-year follow-up of nivolumab in previously treated advanced non-small-cell lung cancer.N Engl JMed,2015,36(17):1675-1684.doi:10.1200/JCO.2017.77.0412
6 Herbst RS,Onn A,Sandler A.Angiogenesis and lung cancer:prognostic and therapeutic implications.J Clin Oncol,2005,23(14):3243-3256.doi:10.1200/JCO.2005.18.853
7 Instructions for bevacizumab injection,amended on July 1,2015.[贝伐珠单抗注射液说明书,修改日期2015年7月1日.]
8 Instructions for recombinant human endostatin injection.Amendment date:19 June,2006.[重组人血管内皮抑制素注射液说明书.修改日期2006年6月19日.]
9 Instructions for Anlotinib Hydrochloride Capsules,approval date 11May,2018.[盐酸安罗替尼胶囊说明书,核准日期2018年5月11日.]
10 Chinese Society of Clinical Oncology(CSCO).Guidelines for Diagnosis and Treatment of Primary Lung Cancer(2018 edition).People's Health Publishing House.[中国临床肿瘤学会(CSCO).原发性肺癌诊疗指南(2018版).人民卫生出版社.]
11 Zhou C,Wu Y L,Chen G,et al.BEYOND:A randomized,doublebl i nd,placebo-cont rol led,multicenter,phase III study of firstline 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.doi:10.1200/JCO.2014.59.4424
12 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.doi:10.1056/NEJMoa061884
13 Reck M,von Pawel J,Zatloukal P,et al.Overall survival with cisplatingemcitabine and bevacizumab or placebo as f irst-line therapy for nonsquamous non-small-cell lung cancer:results from a randomised phase III trial(AVA iL).A nn Oncol,2010,21(9):1804-1809.doi:10.1093/annonc/mdq020
14 Reck M,von Pawel J,Zatloukal P,et al.Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer:AVAil.J Clin Oncol,2009,27(8):1227-1234.doi:10.1200/JCO.2007
15 Langer C,Soria JC.The role of anti-epidermal growth factor receptor and anti-vascular endothelial growth factor therapies in the treatment of non-small-cell lung cancer.Clin Lung Cancer,2010,11(2):82-90.doi:10.3816/CLC.2010.n.011
16 Herbst RS,Johnson DH,Mininberg E,et al.Phase I/II trial evaluating the anti-vascular endothelial grow th factor monoclonal antibody bevacizumab in combination with the HER-1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib for patients with recurrent non-small-cell lung cancer.J Clin Oncol,2005,23(11):2544-2555.doi:10.1200/JCO.2005.02.477
17 Hegde PS,Wallin JJ,Mancao C,et al.Predictive markers of anti-VEGFand emerging role of angiogenesis inhibitors as immunotherapeutics.S e m i n C a n c e r B i o l,2 018,5 2(P t 2):117-1 2 4.d o i:10.1016/j.semcancer.2017.12.002
18 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.doi:10.1056/NEJMoa1716948
19 Spratlin JL,Cohen R B,Eadens M,et al.Phase I pharmacologic and biologic study of ramucir umab(I MC-1121B),a f ully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial grow th factor receptor-2.J Clin Oncol,2010,28(5):780-787.doi:10.1200/JCO.2009.23.7537
20 Hall R D,Le TM,Haggstrom DE,et al.Angiogenesis inhibition as a therapeutic strategy in non-small cell lung cancer(NSCLC).Lancet,2014,384(9944):665-673.doi:10.3978/j.issn.2218-6751.2015.06.09
21 Han B,Li K,Zhao Y,et al.Anlotinib as a third-line therapy in patients with refractory advanced non-small-cell lung cancer:a multicentre,randomised phase II trial(A LTER0302).Br J Cancer,2018,118(5):654-661.doi:10.1038/bjc.2017.478
22 Han B,Li K,Wang Q,et al.Effect of anlotinib as a third-line or further treatment on overall survival of patients with advanced non-small cell lung cancer:The ALTER 0303 phase 3 randomized clinical trial.doi:10.1001/jamaoncol.2018.3039
23 Abdollahi A,Hahnfeldt P,Maercker C,et al.Endostatin’s antiangiogenic signaling network.Mol Cell,2004,13(5):649-663.
24 Patel JD,Socinski MA,Garon EB,et al.PointBreak:a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer.J Clin Oncol,2013,31(34):4349-4357.doi:10.1200/JCO.2012.47.9626
25 Barlesi F,Scherpereel A,R ittmeyer A,et al.Randomized phase IIItrial of maintenance bevacizumab with or without pemetrexed after f irst-line induction w ith bevacizumab,cisplatin,and pemetrexed in advanced nonsquamous non-small-cell lung cancer:AVA PER L(MO22089).J Clin Oncol,2013,31(24):3004-3011.doi:10.1200/JCO.2012.42.3749
26 Mok TS,Hsia TC,Tsai CM,et al.Eff icacy of bevacizumab w ith cisplatin and gemcitabine in Asian patients with advanced or recurrent non-squamous non-small cell lung cancer who have not received prior chemotherapy:a substudy of the Avastin in Lung trial.Asia Pac J Clin Oncol,2011,7 Suppl 2:4-12.doi:10.1111/j.1743-7563.2011.01397.x
27 Behera M,Pillai R N,Owonikoko T K,et al.Bevacizumab in combination with taxane versus non-taxane containing regimens for advanced/metastatic nonsquamous non-small-cell lung cancer:a systematic review.J Thorac Oncol,2015,10(8):1142-1147.
28 Zhou CC,Bai CX,Guan ZZ,et al.Safety and efficacy of first-line bevacizu mab combi nation therapy in Chinese population with advanced non-squamous NSCLC:data of subgroup analyses from MO19390(SAiL)study.Clin Transl Oncol,2014,16(5):463-468.doi:10.1007/s12094-013-1102-5
29 Xing P,Mu Y,Wang Y,et al.Real world study of regimen containing bevacizumab as first-line therapy in Chinese patients with advanced non-small cell lung cancer.Thorac Cancer,2018,9(7):805-813.doi:10.1111/1759-7714.12650
30 Group of Lung Cancer,Societ y of Respirator y Diseases,Chinese A ssociat ion of Lung Cancer Prevention and Treatment.Expert consensus on antiangiogenic drugs for advanced non-small cell lung cancer(2016 edition).Zhonghua Jie He He Hu Xi Za Zhi,2016,39(11):839-849.[中华医学会呼吸病学分会肺癌学组,中国肺癌防治联盟.晚期非小细胞肺癌抗血管生成药物治疗中国呼吸领域专家共识(2016版).中华结核和呼吸杂志,2016,39(11):839-849.]doi:10.3760/cma.j.issn.1001-0939.2016.11.004
31 Cortot AB,Janne PA.Molecular mechanisms of resistance in epidermal growth factor receptor-mutant lung adenocarcinomas.Eur Respir Rev,2014,23(133):356-366.
32 Seto T,Kato T,Nishio M,et al.Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-smallcell lung cancer harbouring EGFR mutations(JO25567):an open-label,randomised,multicentre,phase 2 study.Lancet Oncol,2014,15(11):1236-1244.doi:10.1016/S1470-2045(14)70381-X
33 Yamamoto N,Seto T,Nishio M,et al.Erlotinib plus bevacizumab(EB)versus erlotinib alone(E)as first-line treatment for advanced EGFRmutation-positive non-squamous non-small-cell lung cancer(NSCLC):Survival follow-up results of JO25567.J Clin Oncol,36(5_suppl):9007.doi:10.1200/JCO.2018.36.15_suppl.9007
34 Kato T,Seto T,Nishio M,et al.Erlotinib plus bevacizumab phase IIstudy in patients with advanced non-small-cell lung cancer(JO25567):updated safety results.Drug Saf,2018,41(2):229-237.doi:10.1007/s40264-017-0596-0
35 Saito H,Fukuhara T,Furuya N,et al.Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer(NEJ026):interim analysis of an open-label,randomised,multicentre,phase 3 trial.Lancet Oncol,2019,20(5):625-635.doi:10.1016/S1470-2045(19)30035-X
36 Wang JW,Sun Y,Liu Y Y,et al.Randomized,double-blind,controlled,multicenter phase III clinical study of recombinant human endostatin combined with NP regimen for advanced NSCLC.Zhongguo Fei Ai Za Zhi,2005,8(8):283-290.[王金万,孙燕,刘永煜,等.重组人血管内皮抑素联合NP方案治疗晚期NSCLC随机、双盲、对照、多中心III期临床研究.中国肺癌杂志,2005,8(8):283-290.]doi:10.3779/cjlc.v8i4.1926
37 Attili I,Passaro A,Pavan A,et al.Combination immunotherapy strategies in advanced non-small cell lung cancer(NSCLC):Does biological rationale meet clinical needs?Crit Rev Oncol Hematol,2017,119:30-39.doi:10.1016/j.critrevonc
38 Reck M,Mok TSK,Nishio M,et al.Atezolizumab plus bevacizumab and chemotherapy in non-small-cell lung cancer(IMpower150):key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised,open-label phase 3 trial.Lancet Respir Med,2019,7(5):387-401.
39 Howard W,Michael M,Maen H,et al.Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemot herapy a lone as f i rst-l i ne t reat ment for metastat ic nonsquamous non-small-cell lung cancer(IMpower130):a multicentre,randomised,open-label,phase 3 trial.Lancet Oncol,2019.doi:10.1016/S1470-2045(19)30167-6
40 Nadler E,Yu E,Ravelo A,et al.Bevacizumab treatment to progression after chemot herapy:outcomes from a U.S.com mun it y pract ice network.Oncologist,2011,16(4):486-496.
41 Kosty MP,Wozniak AJ,Jahanzeb M,et al.Effectiveness and safety of post-induction phase bevacizumab treatment for patients with nonsmall-cell lung cancer:results from the AR IES observational cohort study.Target Oncol,2015,10(4):509-516.
42 Takashi S,Koichi A,Takeharu Y,et al.A randomized phase III study of continuous maintenance bevacizumab with or without pemetrexed after induction therapy with carboplatin(Car),pemetrexed(Pem),and bevacizumab(Bev)for advanced non-squamous non-small cell lung cancer(nSQ-NSCLC)without sensitizing EGFR mutations:The COMPASS study(WJOG5610L).ASCO 2019.Abstract 9003.
43 A lex is BC,Clarisse AV,Oliv ier M,et al.Week ly paclita xel plus bevacizumab versus docetaxel as second or third-line treatment in advanced non-squamous nonsmall cell lung cancer(NSCLC):Results from the phase III study IFCT-1103 ULTIM ATE.J Clin Oncol,2016,34(15_suppl):9005.doi:10.1200/JCO.2016.34.15_s uppl.9005
44 Kurishima K,Watanabe H,Ishikawa H,et al.A retrospective study of docetaxel and bevacizumab as a second-or later-line chemotherapy for non-small cell lung cancer.Mol Clin Oncol,2017,7(1):131-134.doi:10.3892/mco.2017.1282
45 Lask in J,CrinòL,Felip E,et al.Safety and efficacy of first-line bevacizumab plus chemotherapy in elderly patients with advanced or recurrent nonsquamous non-small cell lung cancer:safety of avastin in lung trial(MO19390).J Thorac Oncol,2012,7(1):203-211.
46 Wozniak AJ,Kosty MP,Jahanzeb M,et al.Clinical outcomes in elderly patients with advanced non-small cell lung cancer:results from ARIES,a bevacizumab observational cohort study.Clin Oncol(R Coll Radiol),2015,27(4):187-196.
47 Besse B,Lasserre SF,Compton P,et al.Bevacizumab safety in patients with central nervous system metastases.Clin Cancer Res,2010,16(1):269-278.
48 Sandler A,Hirsh V,Reck M,et al.An evidence-based review of the incidence of CNS bleeding with anti-VEGF therapy in non-small cell lung cancer patients with brain metastases.Lung Cancer,2012,78(1):1-7.
49 Besse B,Le Moulec S,Mazières J,et al.Bevacizumab in patients with nonsquamous non-small cell lung cancer and asymptomatic,untreated brain metastases(BR AIN):a nonrandomized,phase II study.Clin Cancer Res,2015,21(8):1896-1903.
50 Du N,Li X,Li F,et al.I ntrapleura l combination t herapy w it h bevacizumab and cisplatin for non-small cell lung cancer-mediated malignant pleural effusion.Oncol Rep,2013,29(6):2332-2340.
51 Qin SK,Yang LQ,Liang J,et al.Intra-pleural injection of recombinant human endostatin and/or cisplatin in treatment of malignant hydrothorax and ascites:A multicenter randomized controlled trial.Lin Chuang Zhong Liu Xue Za Zhi,2017,22(3):193-202.[秦叔逵,杨柳青,梁军,等.腔内应用重组人血管内皮抑制素和/或顺铂治疗恶性胸腹腔积液的前瞻性、随机对照、全国多中心III期临床研究.临床肿瘤学杂志,2017,22(3):193-202.]doi:10.3969/j.issn.1009-0460.2017.03.001
52 Li M,K roetz DL.Bevacizumab-induced hy pertension:Clinical presentation and molecular understanding.Pharmacol Ther,2018,182:152-160.doi:10.1016/j.pharmthera.2017.08.012
53 Brandes A A,Bartolotti M,Tosoni A,et al.Practical management of bevacizumab-related toxicities in glioblastoma.Oncologist,2015,20(2):166-175.doi:10.1634/theoncologist.2014-0330
2 http://gco.iarc.fr/today/data/factsheets/populations/160-china-factsheets.pdf.
3 Cufer T,Knez L.Update on systemic therapy of advanced non-smallcell lung cancer.Expert Rev Anticancer Ther,2014,14(10):1189-1203.doi:10.1586/14737140.2014.940327
4 Han BH.Epidemiology of lung cancer by molecular subtype in China.Presented by Baohui Han,16th WCLC,2015.
5 Gettinger S,Horn L,Jackman D,et al.Five-year follow-up of nivolumab in previously treated advanced non-small-cell lung cancer.N Engl JMed,2015,36(17):1675-1684.doi:10.1200/JCO.2017.77.0412
6 Herbst RS,Onn A,Sandler A.Angiogenesis and lung cancer:prognostic and therapeutic implications.J Clin Oncol,2005,23(14):3243-3256.doi:10.1200/JCO.2005.18.853
7 Instructions for bevacizumab injection,amended on July 1,2015.[贝伐珠单抗注射液说明书,修改日期2015年7月1日.]
8 Instructions for recombinant human endostatin injection.Amendment date:19 June,2006.[重组人血管内皮抑制素注射液说明书.修改日期2006年6月19日.]
9 Instructions for Anlotinib Hydrochloride Capsules,approval date 11May,2018.[盐酸安罗替尼胶囊说明书,核准日期2018年5月11日.]
10 Chinese Society of Clinical Oncology(CSCO).Guidelines for Diagnosis and Treatment of Primary Lung Cancer(2018 edition).People's Health Publishing House.[中国临床肿瘤学会(CSCO).原发性肺癌诊疗指南(2018版).人民卫生出版社.]
11 Zhou C,Wu Y L,Chen G,et al.BEYOND:A randomized,doublebl i nd,placebo-cont rol led,multicenter,phase III study of firstline 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.doi:10.1200/JCO.2014.59.4424
12 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.doi:10.1056/NEJMoa061884
13 Reck M,von Pawel J,Zatloukal P,et al.Overall survival with cisplatingemcitabine and bevacizumab or placebo as f irst-line therapy for nonsquamous non-small-cell lung cancer:results from a randomised phase III trial(AVA iL).A nn Oncol,2010,21(9):1804-1809.doi:10.1093/annonc/mdq020
14 Reck M,von Pawel J,Zatloukal P,et al.Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer:AVAil.J Clin Oncol,2009,27(8):1227-1234.doi:10.1200/JCO.2007
15 Langer C,Soria JC.The role of anti-epidermal growth factor receptor and anti-vascular endothelial growth factor therapies in the treatment of non-small-cell lung cancer.Clin Lung Cancer,2010,11(2):82-90.doi:10.3816/CLC.2010.n.011
16 Herbst RS,Johnson DH,Mininberg E,et al.Phase I/II trial evaluating the anti-vascular endothelial grow th factor monoclonal antibody bevacizumab in combination with the HER-1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib for patients with recurrent non-small-cell lung cancer.J Clin Oncol,2005,23(11):2544-2555.doi:10.1200/JCO.2005.02.477
17 Hegde PS,Wallin JJ,Mancao C,et al.Predictive markers of anti-VEGFand emerging role of angiogenesis inhibitors as immunotherapeutics.S e m i n C a n c e r B i o l,2 018,5 2(P t 2):117-1 2 4.d o i:10.1016/j.semcancer.2017.12.002
18 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.doi:10.1056/NEJMoa1716948
19 Spratlin JL,Cohen R B,Eadens M,et al.Phase I pharmacologic and biologic study of ramucir umab(I MC-1121B),a f ully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial grow th factor receptor-2.J Clin Oncol,2010,28(5):780-787.doi:10.1200/JCO.2009.23.7537
20 Hall R D,Le TM,Haggstrom DE,et al.Angiogenesis inhibition as a therapeutic strategy in non-small cell lung cancer(NSCLC).Lancet,2014,384(9944):665-673.doi:10.3978/j.issn.2218-6751.2015.06.09
21 Han B,Li K,Zhao Y,et al.Anlotinib as a third-line therapy in patients with refractory advanced non-small-cell lung cancer:a multicentre,randomised phase II trial(A LTER0302).Br J Cancer,2018,118(5):654-661.doi:10.1038/bjc.2017.478
22 Han B,Li K,Wang Q,et al.Effect of anlotinib as a third-line or further treatment on overall survival of patients with advanced non-small cell lung cancer:The ALTER 0303 phase 3 randomized clinical trial.doi:10.1001/jamaoncol.2018.3039
23 Abdollahi A,Hahnfeldt P,Maercker C,et al.Endostatin’s antiangiogenic signaling network.Mol Cell,2004,13(5):649-663.
24 Patel JD,Socinski MA,Garon EB,et al.PointBreak:a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer.J Clin Oncol,2013,31(34):4349-4357.doi:10.1200/JCO.2012.47.9626
25 Barlesi F,Scherpereel A,R ittmeyer A,et al.Randomized phase IIItrial of maintenance bevacizumab with or without pemetrexed after f irst-line induction w ith bevacizumab,cisplatin,and pemetrexed in advanced nonsquamous non-small-cell lung cancer:AVA PER L(MO22089).J Clin Oncol,2013,31(24):3004-3011.doi:10.1200/JCO.2012.42.3749
26 Mok TS,Hsia TC,Tsai CM,et al.Eff icacy of bevacizumab w ith cisplatin and gemcitabine in Asian patients with advanced or recurrent non-squamous non-small cell lung cancer who have not received prior chemotherapy:a substudy of the Avastin in Lung trial.Asia Pac J Clin Oncol,2011,7 Suppl 2:4-12.doi:10.1111/j.1743-7563.2011.01397.x
27 Behera M,Pillai R N,Owonikoko T K,et al.Bevacizumab in combination with taxane versus non-taxane containing regimens for advanced/metastatic nonsquamous non-small-cell lung cancer:a systematic review.J Thorac Oncol,2015,10(8):1142-1147.
28 Zhou CC,Bai CX,Guan ZZ,et al.Safety and efficacy of first-line bevacizu mab combi nation therapy in Chinese population with advanced non-squamous NSCLC:data of subgroup analyses from MO19390(SAiL)study.Clin Transl Oncol,2014,16(5):463-468.doi:10.1007/s12094-013-1102-5
29 Xing P,Mu Y,Wang Y,et al.Real world study of regimen containing bevacizumab as first-line therapy in Chinese patients with advanced non-small cell lung cancer.Thorac Cancer,2018,9(7):805-813.doi:10.1111/1759-7714.12650
30 Group of Lung Cancer,Societ y of Respirator y Diseases,Chinese A ssociat ion of Lung Cancer Prevention and Treatment.Expert consensus on antiangiogenic drugs for advanced non-small cell lung cancer(2016 edition).Zhonghua Jie He He Hu Xi Za Zhi,2016,39(11):839-849.[中华医学会呼吸病学分会肺癌学组,中国肺癌防治联盟.晚期非小细胞肺癌抗血管生成药物治疗中国呼吸领域专家共识(2016版).中华结核和呼吸杂志,2016,39(11):839-849.]doi:10.3760/cma.j.issn.1001-0939.2016.11.004
31 Cortot AB,Janne PA.Molecular mechanisms of resistance in epidermal growth factor receptor-mutant lung adenocarcinomas.Eur Respir Rev,2014,23(133):356-366.
32 Seto T,Kato T,Nishio M,et al.Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-smallcell lung cancer harbouring EGFR mutations(JO25567):an open-label,randomised,multicentre,phase 2 study.Lancet Oncol,2014,15(11):1236-1244.doi:10.1016/S1470-2045(14)70381-X
33 Yamamoto N,Seto T,Nishio M,et al.Erlotinib plus bevacizumab(EB)versus erlotinib alone(E)as first-line treatment for advanced EGFRmutation-positive non-squamous non-small-cell lung cancer(NSCLC):Survival follow-up results of JO25567.J Clin Oncol,36(5_suppl):9007.doi:10.1200/JCO.2018.36.15_suppl.9007
34 Kato T,Seto T,Nishio M,et al.Erlotinib plus bevacizumab phase IIstudy in patients with advanced non-small-cell lung cancer(JO25567):updated safety results.Drug Saf,2018,41(2):229-237.doi:10.1007/s40264-017-0596-0
35 Saito H,Fukuhara T,Furuya N,et al.Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer(NEJ026):interim analysis of an open-label,randomised,multicentre,phase 3 trial.Lancet Oncol,2019,20(5):625-635.doi:10.1016/S1470-2045(19)30035-X
36 Wang JW,Sun Y,Liu Y Y,et al.Randomized,double-blind,controlled,multicenter phase III clinical study of recombinant human endostatin combined with NP regimen for advanced NSCLC.Zhongguo Fei Ai Za Zhi,2005,8(8):283-290.[王金万,孙燕,刘永煜,等.重组人血管内皮抑素联合NP方案治疗晚期NSCLC随机、双盲、对照、多中心III期临床研究.中国肺癌杂志,2005,8(8):283-290.]doi:10.3779/cjlc.v8i4.1926
37 Attili I,Passaro A,Pavan A,et al.Combination immunotherapy strategies in advanced non-small cell lung cancer(NSCLC):Does biological rationale meet clinical needs?Crit Rev Oncol Hematol,2017,119:30-39.doi:10.1016/j.critrevonc
38 Reck M,Mok TSK,Nishio M,et al.Atezolizumab plus bevacizumab and chemotherapy in non-small-cell lung cancer(IMpower150):key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised,open-label phase 3 trial.Lancet Respir Med,2019,7(5):387-401.
39 Howard W,Michael M,Maen H,et al.Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemot herapy a lone as f i rst-l i ne t reat ment for metastat ic nonsquamous non-small-cell lung cancer(IMpower130):a multicentre,randomised,open-label,phase 3 trial.Lancet Oncol,2019.doi:10.1016/S1470-2045(19)30167-6
40 Nadler E,Yu E,Ravelo A,et al.Bevacizumab treatment to progression after chemot herapy:outcomes from a U.S.com mun it y pract ice network.Oncologist,2011,16(4):486-496.
41 Kosty MP,Wozniak AJ,Jahanzeb M,et al.Effectiveness and safety of post-induction phase bevacizumab treatment for patients with nonsmall-cell lung cancer:results from the AR IES observational cohort study.Target Oncol,2015,10(4):509-516.
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