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Journal of Cancer Research and Clinical Oncology

Published in:

01-03-2020 | NSCLC | Review – Clinical Oncology

New advances in antiangiogenic combination therapeutic strategies for advanced non-small cell lung cancer

Authors: Huiping Qiang, Qing Chang, Jianlin Xu, Jialin Qian, Yanwei Zhang, Yuqiong Lei, Baohui Han, Tianqing Chu

Published in: Journal of Cancer Research and Clinical Oncology | Issue 3/2020

Abstract

Purpose

Tumor growth relies on the sufficient blood supply and continuously requires new blood vessels to maintain, which lead to vascular abnormalities (Folkman, N Engl J Med 285:1182–1186, 1971). Antiangiogenic therapy has emerged with the goal of normalizing vasculature and tumor microenvironment (TME). Some antiangiogenic therapies combined with chemotherapy, targeted therapy or immunotherapy have been approved for clinical application. In this review, we summarize the recent advances of antiangiogenic combination therapeutic strategies in advanced NSCLC.

Methods

References of this review are searched through PubMed and EMBASE and the abstracts of cancer conferences. The ClinicalTrials.gov database was used for relative trials.

Results

Based on different mechanisms, antiangiogenic agents can be divided into monoclonal antibodies (mAbs), which mainly include bevacizumab and ramucirumab, and multi-target antiangiogenic tyrosine kinase inhibitors (TKIs) which include sunitinib, sorafenib, nintedanib, apatinib, anlotinib, fruquintinib, etc. In recent years, a number of large clinical studies have shown that antiangiogenic agents have conferred a significant overall survival (OS) benefit to patients with advanced non-small cell lung cancer (NSCLC). More and more evidences confirm that the combination of antiangiogenic agents with chemotherapy, targeted therapy and immunotherapy can improve the effect and prolong the survival of NSCLC patients. However, many problems about the application of antiangiogenic agents on advanced NSCLC patients still need to be explored. For example, the combination therapy of multi-target antiangiogenic agents is just beginning, and the biomarkers are not clear.

Conclusions

Antiangiogenic agents can achieve therapeutic benefit in advanced NSCLC patients and the combination of chemotherapy, targeted therapy or immunotherapy can lead to synergistic effect. However, exploring the best combination therapy and efficacy-related biomarkers needs further study.

Baggstrom MQ, Socinski MA, Wang XF et al (2017) Maintenance sunitinib following initial platinum-based combination chemotherapy in advanced-stage IIIB/IV non-small cell lung cancer: a randomized, double-blind, placebo-controlled phase III study-CALGB 30607 (Alliance). J Thorac Oncol 12:843–849. https://doi.org/10.1016/j.jtho.2017.01.022 CrossRefPubMedPubMedCentral

Barlesi F, Scherpereel A, Rittmeyer A et al (2013) Randomized phase III trial of maintenance bevacizumab with or without pemetrexed after first-line induction with bevacizumab, cisplatin, and pemetrexed in advanced nonsquamous non-small-cell lung cancer: AVAPERL (MO22089). J Clin Oncol 31:3004–3011. https://doi.org/10.1200/jco.2012.42.3749 CrossRefPubMed

Bouzin C, Brouet A, De Vriese J, Dewever J, Feron O (2007) Effects of vascular endothelial growth factor on the lymphocyte-endothelium interactions: identification of caveolin-1 and nitric oxide as control points of endothelial cell anergy. J Immunol 178:1505–1511. https://doi.org/10.4049/jimmunol.178.3.1505 CrossRefPubMed

Bray F, Ferlay J, Soerjomataram I et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424. https://doi.org/10.3322/caac.21492 CrossRefPubMed

de Boer RH, Arrieta Ó, Yang CH et al (2011) Vandetanib plus pemetrexed for the second-line treatment of advanced non-small-cell lung cancer: a randomized, double-blind Phase III trial. J Clin Oncol 29:1067–1074. https://doi.org/10.1200/jco.2010.29.5717 CrossRefPubMed

De Luca A, Carotenuto A, Rachiglio A et al (2008) The role of the EGFR signaling in tumor microenvironment. J Cell Physiol 214:559–567. https://doi.org/10.1002/jcp.21260 CrossRefPubMed

Doebele RC, Spigel D, Tehfe M et al (2015) Phase 2, randomized, open-label study of ramucirumab in combination with first-line pemetrexed and platinum chemotherapy in patients with nonsquamous, advanced/metastatic non-small cell lung cancer. Cancer 121:883–892. https://doi.org/10.1002/cncr.29132 CrossRefPubMed

Finke JH, Rini B, Ireland J et al (2008) Sunitinib reverses type-1 immune suppression and decreases T-regulatory cells in renal cell carcinoma patients. Clin Cancer Res 14:6674–6682. https://doi.org/10.1158/1078-0432.CCR-07-5212 CrossRefPubMed

Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186. https://doi.org/10.1056/nejm197111182852108 CrossRefPubMed

Folkman J (1972) Anti-angiogenesis: new concept for therapy of solid tumors. Ann Surg 175:409–416. https://doi.org/10.1097/00000658-197203000-00014 CrossRefPubMedPubMedCentral

Fontanella C, Ongaro E, Bolzonello S et al (2014) Clinical advances in the development of novel VEGFR2 inhibitors. Ann Transl Med 2:123. https://doi.org/10.3978/j.issn.2305-5839.2014.08.14 CrossRefPubMedPubMedCentral

Fukumura D, Kloepper J, Amoozgar Z, Duda DG, Jain RK (2018) Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges. Nat Rev Clin Oncol 15:325–340. https://doi.org/10.1038/nrclinonc.2018.29 CrossRefPubMedPubMedCentral

Furuya N, Fukuhara T, Saito H et al (2018) Phase III study comparing bevacizumab plus erlotinib to erlotinib in patients with untreated NSCLC harboring activating EGFR mutations: NEJ026. J Clin Oncol 36:9006. https://doi.org/10.1200/jco.2018.36.15_suppl.9006 CrossRef

Gabrilovich DI, Chen HL, Girgis KR et al (1996) Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med 2:1096–1103. https://doi.org/10.1038/nm1096-1096 CrossRefPubMed

Gabrilovich D, Ishida T, Oyama T et al (1998) Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood 92:4150–4166CrossRefPubMed

Garon EB, Ciuleanu TE, Arrieta O et al (2014) Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet 384:665–673. https://doi.org/10.1016/s0140-6736(14)60845-x CrossRefPubMed

Gridelli C, de Castro CJ, Dingemans AC et al (2018) Safety and efficacy of bevacizumab plus standard-of-care treatment beyond disease progression in patients with advanced non-small cell lung cancer the AvaALL randomized clinical trial. JAMA Oncol 4:e183486. https://doi.org/10.1001/jamaoncol.2018.3486 CrossRefPubMedPubMedCentral

Hall RD, Le TM, Haggstrom DE, Gentzler RD (2015) Angiogenesis inhibition as a therapeutic strategy in non-small cell lung cancer (NSCLC). Transl Lung Cancer Res 4:515–523. https://doi.org/10.3978/j.issn.2218-6751.2015.06.09 CrossRefPubMedPubMedCentral

Han B et al (2019) WCLC Abstract P1.01.95

Han B, Li K, Zhao Y et al (2018a) Anlotinib as a third-line therapy in patients with refractory advanced non-small-cell lung cancer: a multicentre, randomised phase II trial (ALTER0302). Br J Cancer 118:654–661. https://doi.org/10.1038/bjc.2017.478 CrossRefPubMedPubMedCentral

Han B, Li K, Wang Q et al (2018b) 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. JAMA Oncol 4:1569–1575. https://doi.org/10.1001/jamaoncol.2018.3039 CrossRefPubMedPubMedCentral

Herbst RS, Ansari R, Bustin F et al (2011) Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial. Lancet 377:1846–1854. https://doi.org/10.1016/s0140-6736(11)60545-x CrossRefPubMedPubMedCentral

Herbst RS, Arkenau HT, Santana-Davila R et al (2019a) Ramucirumab plus pembrolizumab in patients with previously treated advanced non-small-cell lung cancer, gastro-oesophageal cancer, or urothelial carcinomas (JVDF): a multicohort, non-randomised, open-label, phase 1a/b trial. Lancet Oncol 20:1109–1123. https://doi.org/10.1016/S1470-2045(19)30458-9 CrossRefPubMed

Herbst RS, Arkenau HT, Bendell J et al (2019b) Phase I expansion cohort of ramucirumab plus pembrolizumab in advanced treatment-naive non-small cell lung cancer (JVDF). WCLC meeting, Abstract MA14.07

Holleb AI, Folkman J (1972) Tumor angiogenesis. CA Cancer J Clin 22:226–229. https://doi.org/10.3322/canjclin.22.4.226 CrossRefPubMed

Ichihara E, Hotta K, Nogami N et al (2015) Phase II trial of gefitinib in combination with bevacizumab as first-line therapy for advanced non-small cell lung cancer with activating EGFR gene mutations: the Okayama Lung Cancer Study Group Trial 1001. J Thorac Oncol 10:486–491. https://doi.org/10.1097/jto.0000000000000434 CrossRefPubMed

Johnson BE, Kabbinavar F, Fehrenbacher L et al (2013) ATLAS: randomized, double-blind, placebo-controlled, phase IIIB trial comparing bevacizumab therapy with or without erlotinib, after completion of chemotherapy, with bevacizumab for first-line treatment of advanced non-small-cell Lung cancer. J Clin Oncol 31:3926–3934. https://doi.org/10.1200/JCO.2012.47.3983 CrossRefPubMed

Jung YD, Mansfield PF, Akagi M et al (2002) Effects of combination anti-vascular endothelial growth factor receptor and anti-epidermal growth factor receptor therapies on the growth of gastric cancer in a nude mouse model. Eur J Cancer 38:1133–1140. https://doi.org/10.1016/s0959-8049(02)00013-8 CrossRefPubMed

Kabbinavar F, Fehrenbacher L, Hainsworth J et al (2014) Biomarker analyses from a randomized, placebo-controlled, phase IIIb trial comparing bevacizumab with or without erlotinib as maintenance therapy for the treatment of advanced non-small-cell lung cancer (ATLAS). J Thorac Oncol 9:1411–1417. https://doi.org/10.1097/JTO.0000000000000274 CrossRefPubMed

Krzywinska E, Kantari-Mimoun C, Kerdiles Y et al (2017) Loss of HIF-1α in natural killer cells inhibits tumour growth by stimulating non-productive angiogenesis. Nat Commun 8:1597. https://doi.org/10.1038/s41467-017-01599-w CrossRefPubMedPubMedCentral

Li B, Lalani AS, Harding TC et al (2006) Vascular endothelial growth factor blockade reduces intratumoral regulatory T cells and enhances the efficacy of a GM-CSF-secreting cancer immunotherapy. Clin Cancer Res 12:6808–6816. https://doi.org/10.1158/1078-0432.CCR-06-1558 CrossRefPubMed

Lin MI, Sessa WC (2004) Antiangiogenic therapy: creating a unique “window” of opportunity. Cancer Cell 6:529–531. https://doi.org/10.1016/j.ccr.2004.12.003 CrossRefPubMed

Lu S, Zhou J, Niu X, Chen M, Hua Y, Su W (2017) P.301-070 a phase II study of fruquintinib in combination with gefitinib in stage IIIb/IV NSCLC patients harboring EGFR activating mutations. J Thorac Oncol 12:S2228. https://doi.org/10.1016/j.jtho.2017.09.1511 CrossRef

Lu J, Zhong H, Chu T et al (2019) Role of anlotinib-induced CCL2 decrease in anti-angiogenesis and response prediction for nonsmall cell lung cancer therapy. Eur Respir J 53:1801562. https://doi.org/10.1183/13993003.01562-2018 CrossRefPubMed

Manegold C, Dingemans AC, Gray JE et al (2017) The potential of combined immunotherapy and antiangiogenesis for the synergistic treatment of advanced NSCLC. J Thorac Oncol 12:194–207. https://doi.org/10.1016/j.jtho.2016.10.003 CrossRefPubMed

Masuda C, Yanagisawa M, Yorozu K et al (2017) Bevacizumab counteracts VEGF-dependent resistance to erlotinib in an EGFR-mutated NSCLC xenograft model. Int J Oncol 51:425–434. https://doi.org/10.3892/ijo.2017.4036 CrossRefPubMedPubMedCentral

Miller KD, Siegel RL, Lin CC et al (2016) Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin 66:271–289. https://doi.org/10.3322/caac.21349 CrossRefPubMed

Mok TS, Hsia TC, Tsai CM et al (2011) Efficacy of bevacizumab with 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 7:4–12. https://doi.org/10.1111/j.1743-7563.2011.01397.x CrossRefPubMed

Mok T, Gorbunova V, Juhasz E et al (2014) A correlative biomarker analysis of the combination of bevacizumab and carboplatin-based chemotherapy for advanced nonsquamous non-small-cell lung cancer: results of the phase II randomized ABIGAIL study (BO21015). J Thorac Oncol 9:848–855. https://doi.org/10.1097/JTO.0000000000000160 CrossRefPubMed

Molina JR, Dy GK, Foster NR et al (2011) A randomized phase II study of pemetrexed (PEM) with or without sorafenib (S) as second-line therapy in advanced non-small cell lung cancer (NSCLC) of nonsquamous histology: NCCTG N0626 study. J Clin Oncol 29:7513. https://doi.org/10.1200/jco.2011.29.15_suppl.7513 CrossRef

Motz GT, Santoro SP, Wang LP et al (2014) Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors. Nat Med 20:607–615. https://doi.org/10.1038/nm.3541 CrossRefPubMedPubMedCentral

Nakagawa K et al (2019) RELAY: a multinational, double-blind, randomized Phase 3 study of erlotinib (ERL) in combination with ramucirumab (RAM) or placebo (PL) in previously untreated patients with epidermal growth factor receptor mutation-positive (EGFRm) metastatic non-small cell lung cancer (NSCLC). ASCO meeting, Abstract 9000

Nakahara Y, Kato T, Isomura R et al (2019) A multicenter, open label, randomized phase II study of osimertinib plus ramucirumab versus osimertinib alone as initial chemotherapy for EGFR mutation-positive non-squamous non-small cell lung cancer: TORG1833. J Clin Oncol 37(15_suppl):TPS9120CrossRef

Ninomiya T, Ishikawa N, Inoue K et al (2019) Phase 2 study of afatinib alone or combined with bevacizumab in chemonaive patients with advanced non-small-cell lung cancer harboring EGFR mutations: AfaBev-CS study protocol. Clin Lung Cancer 20:134–138. https://doi.org/10.1016/j.cllc.2018.10.008 CrossRefPubMed

Paz-Ares LG, Biesma B, Heigener D et al (2012) Phase III, randomized, double-blind, placebo-controlled trial of gemcitabine/cisplatin alone or with sorafenib for the first-line treatment of advanced, nonsquamous non-small-cell lung cancer. J Clin Oncol 30:3084–3092. https://doi.org/10.1200/jco.2011.39.7646 CrossRefPubMed

Perdrizet K, Leighl NB (2019) The role of angiogenesis inhibitors in the era of immune checkpoint inhibitors and targeted therapy in metastatic non-small cell lung cancer. Curr Treat Options Oncol 20:21. https://doi.org/10.1007/s11864-019-0617-6 CrossRefPubMed

Ramalingam SS, Dahlberg SE, Belani CP et al (2019) Pemetrexed, bevacizumab, or the combination as maintenance therapy for advanced nonsquamous non–small-cell lung cancer: ECOG-ACRIN 5508. J Clin Oncol 37(26):2360–2367CrossRefPubMedPubMedCentral

Reck M, von Pawel J, Zatloukal P et al (2009) 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 27:1227–1234. https://doi.org/10.1200/jco.2007.14.5466 CrossRefPubMed

Reck M, von Pawel J, Zatloukal P et al (2010) Overall survival with cisplatin–gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL). Ann Oncol 21:1804–1809. https://doi.org/10.1093/annonc/mdq020 CrossRefPubMedPubMedCentral

Reck M, Kaiser R, Mellemgaard A et al (2014) Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol 15:143–155. https://doi.org/10.1016/s1470-2045(13)70586-2 CrossRefPubMed

Reck M, Mok TSK, Nishio M et al (2019) 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 7:387–401. https://doi.org/10.1016/s2213-2600(19)30084-0 CrossRefPubMed

Rizvi NA, Antonia SJ, Shepherd FA et al (2014) Nivolumab (Anti-PD-1; BMS-936558, ONO-4538) maintenance as monotherapy or in combination with bevacizumab (BEV) for non-small cell lung cancer (NSCLC) previously treated with chemotherapy. Int J Radiat Oncol Biol Phys. https://doi.org/10.1016/j.ijrobp.2014.08.206 CrossRef

Saito H, Fukuhara T, Furuya N et al (2019) 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 20:625–635. https://doi.org/10.1016/s1470-2045(19)30035-x CrossRefPubMed

Sandler A, Gray R, Perry MC et al (2006) Paclitaxel–carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542–2550. https://doi.org/10.1056/nejmoa061884 CrossRefPubMed

Scagliotti G, Novello S, von Pawel J et al (2010) Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. J Clin Oncol 28:1835–1842. https://doi.org/10.1200/jco.2009.26.1321 CrossRefPubMed

Scagliotti GV, Krzakowski M, Szczesna A et al (2012) Sunitinib plus erlotinib versus placebo plus erlotinib in patients with previously treated advanced non-small-cell lung cancer: a phase III trial. J Clin Oncol 30:2070–2078. https://doi.org/10.1200/jco.2011.39.2993 CrossRefPubMed

Schwaederle M, Lazar V, Validire P et al (2015) VEGF—a expression correlates with TP53 mutations in non-small cell lung cancer: implications for antiangiogenesis therapy. Cancer Res 75:1187–1190. https://doi.org/10.1158/0008-5472.CAN-14-2305 CrossRefPubMed

Seto T, Kato T, Nishio M et al (2014) Erlotinib alone or with Bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol 15:1236–1244. https://doi.org/10.1016/s1470-2045(14)70381-x CrossRefPubMed

Seto T, Azuma K, Yamanaka T et al (2019) A randomized phase III study of continuous maintenance bevacizumab with or without pemetrexed after induction therapy with carboplatin (Car), pemetrexed (Pem), and bevacizumab (Bem) for advanced nonsquamous non–small cell lung cancer (nSQ-NSCLC) without sensitizing EGFRmutations: the COMPASS study (WJOG5610L). J Clin Oncol 37(suppl; abstr 9003)

Shiraishi Y, Daga H, Ikeda S et al (2019) A multicenter, open label, randomized phase III study of atezolizumab with platinum-pemetrexed and with or without bevacizumab for patients with advanced nonsquamous non-small cell lung cancer (WJOG11218L APPLE Study). J Clin Oncol 37(15_suppl):TPS9125CrossRef

Socinski MA, Jotte RM, Cappuzzo F et al (2018a) Overall survival (OS) analysis of IMpower150, a randomized Ph 3 study of atezolizumab (atezo) + chemotherapy (chemo) ± bevacizumab (bev) vs chemo + bev in 1 L nonsquamous (NSQ) NSCLC. J Clin Oncol 36:9002CrossRef

Socinski MA, Jotte RM, Cappuzzo F et al (2018b) Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med 378:2288–2301. https://doi.org/10.1056/NEJMoa1716948 CrossRefPubMed

Tabernero J (2007) The role of VEGF and EGFR inhibition: implications for combining anti-VEGF and anti-EGFR agents. Mol Cancer Res 5:203–220. https://doi.org/10.1158/1541-7786.MCR-06-0404 CrossRefPubMed

Tao L, Huang G, Shi S, Chen L (2014) Bevacizumab improves the antitumor efficacy of adoptive cytokine-induced killer cells therapy in non-small cell lung cancer models. Med Oncol 31:777. https://doi.org/10.1007/s12032-013-0777-3 CrossRefPubMed

Terme M, Pernot S, Marcheteau E et al (2013) VEGFA-VEGFR pathway blockade inhibits tumor-induced regulatory T-cell proliferation in colorectal cancer. Cancer Res 73:539–549. https://doi.org/10.1158/0008-5472.CAN-12-2325 CrossRefPubMed

Tian S, Quan H, Xie C et al (2011) YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo. Cancer Sci 102:1374–1380. https://doi.org/10.1111/j.1349-7006.2011.01939.x CrossRefPubMed

Uchino J, Nakao A, Tamiya N et al (2018) Treatment rationale and design of the SPIRAL study: a phase II trial of osimertinib in elderly epidermal growth factor receptor T790M-positive nonsmall-cell lung cancer patients who progressed during prior EGFR-TKI treatment. Medicine (Baltimore) 97:e11081. https://doi.org/10.1097/md.0000000000011081 CrossRef

Wang J, Chen J, Guo Y, Wang B, Chu H (2017) Strategies targeting angiogenesis in advanced non-small cell lung cancer. Oncotarget 8:53854–53872. https://doi.org/10.18632/oncotarget.17957 CrossRefPubMedPubMedCentral

Yamamoto N, Seto T, Nishio M et al (2018) Erlotinib plus bevacizumab (EB) versus erlotinib alone (E) as first-line treatment for advanced EGFR mutation–positive non-squamous non-small-cell lung cancer (NSCLC): survival follow-up results of JO25567. J Clin Oncol 36:9007. https://doi.org/10.1200/jco.2018.36.15_suppl.9007 CrossRef

Yasuda S, Sho M, Yamato I et al (2013) Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2 (VEGFR2) induces synergistic anti-tumour effect in vivo. Clin Exp Immunol 172:500–506. https://doi.org/10.1111/cei.12069 CrossRefPubMedPubMedCentral

Yu HA, Kim R, Makhnin A et al (2019) A phase 1/2 study of osimertinib and bevacizumab as initial treatment for patients with metastatic EGFR-mutant lung cancers. J Clin Oncol 37(suppl:abstr 9086)

Zhao YY, Xue C, Jiang W et al (2012) Predictive value of intratumoral microvascular density in patients with advanced non-small cell lung cancer receiving chemotherapy plus bevacizumab. J Thorac Oncol 7:71–75. https://doi.org/10.1097/JTO.0b013e31823085f4 CrossRefPubMed

Zhou C, Wu YL, Chen G et al (2015) 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 33:2197–2204. https://doi.org/10.1200/jco.2014.59.4424 CrossRefPubMed

Zhou C, Gao GH, Wang YN et al (2019a) Efficacy of PD-1 monoclonal antibody SHR-1210 plus apatinib in patients with advanced nonsquamous NSCLC with wild-type EGFR and ALK. ASCO meeting, Abstract 9073

Zhou Q, Wu Y, Cheng Y et al (2019b) CTONG 1509: Phase III study of bevacizumab with or without erlotinib in untreated Chinese patients with advanced EGFR-mutated NSCLC (ID 3200). ESMO meeting, Abstract 1480

Title: New advances in antiangiogenic combination therapeutic strategies for advanced non-small cell lung cancer
Authors: Huiping Qiang
Qing Chang
Jianlin Xu
Jialin Qian
Yanwei Zhang
Yuqiong Lei
Baohui Han
Tianqing Chu
Publication date: 01-03-2020
Publisher: Springer Berlin Heidelberg
Keywords: NSCLC
NSCLC
Targeted Therapy
Erlotinib
Bevacizumab
Ramucirumab
Cytostatic Therapy
Published in: Journal of Cancer Research and Clinical Oncology / Issue 3/2020
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-020-03129-6

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