An overview of angiogenesis inhibitors in Phase II studies for non-small-cell lung cancer

Bibliography

• Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000;100(1):57–70
   PubMed Web of Science ®Google Scholar
• Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144(5):646–74
   PubMed Web of Science ®Google Scholar
• Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer 2003;3(6):401–10
   PubMed Web of Science ®Google Scholar
• Baeriswyl V, Christofori G. The angiogenic switch in carcinogenesis. Semin Cancer Biol 2009;19(5):329–37
   PubMed Web of Science ®Google Scholar
• Raica M, Cimpean AM, Ribatti D. Angiogenesis in pre-malignant conditions. Eur J Cancer 2009;45(11):1924–34
   PubMed Web of Science ®Google Scholar
• Ferrara N. Vascular endothelial growth factor. Arterioscler Thromb Vasc Biol 2009;29(6):789–91
   PubMed Web of Science ®Google Scholar
• Mac Gabhann F, Popel AS. Systems biology of vascular endothelial growth factors. Microcirculation 2008;15(8):715–38
   PubMed Web of Science ®Google Scholar
• Lieu C, Heymach J, Overman M, et al. Beyond VEGF: inhibition of the fibroblast growth factor pathway and antiangiogenesis. Clinical Cancer Res 2011;17(19):6130–9
   PubMed Web of Science ®Google Scholar
• Kono SA, Heasley LE, Doebele RC, et al. Adding to the mix: fibroblast growth factor and platelet-derived growth factor receptor pathways as targets in non-small cell lung cancer. Curr Cancer Drug Targets 2012;12(2):107–23
   PubMed Web of Science ®Google Scholar
• Ribatti D. Endogenous inhibitors of angiogenesis: a historical review. Leuk Res 2009;33(5):638–44
   PubMed Web of Science ®Google Scholar
• Fontanini G, Lucchi M, Vignati S, et al. Angiogenesis as a prognostic indicator of survival in non-small-cell lung carcinoma: a prospective study. J Natl Cancer Inst 1997;89(12):881–6
   PubMed Web of Science ®Google Scholar
• Salgia R. Prognostic significance of angiogenesis and angiogenic growth factors in nonsmall cell lung cancer. Cancer 2011;117(17):3889–99
   PubMed Web of Science ®Google Scholar
• 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):2542–50
   PubMed Web of Science ®Google Scholar
• Reck M, Kaiser R, Mellemgaard A, et al. 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 2014;15(2):143–55
   PubMed Web of Science ®Google Scholar
• Garon EB, Ciuleanu TE, Arrieta O, et al. 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 2014;384(9944):665–73
   PubMed Web of Science ®Google Scholar
• Paz-Ares LG, Biesma B, Heigener D, et al. 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 2012;30(25):3084–92
   PubMed Web of Science ®Google Scholar
• Scagliotti G, Novello S, von Pawel J, et al. Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. J Clin Oncol 2010;28(11):1835–42
   PubMed Web of Science ®Google Scholar
• Scagliotti GV, Vynnychenko I, Park K, et al. International, randomized, placebo-controlled, double-blind phase III study of motesanib plus carboplatin/paclitaxel in patients with advanced nonsquamous non-small-cell lung cancer: MONET1. J Clin Oncol 2012;30(23):2829–36
   PubMed Web of Science ®Google Scholar
• Lara PNJr, Douillard JY, Nakagawa K, et al. Randomized phase III placebo-controlled trial of carboplatin and paclitaxel with or without the vascular disrupting agent vadimezan (ASA404) in advanced non-small-cell lung cancer. J Clin Oncol 2011;29(22):2965–71
   PubMed Web of Science ®Google Scholar
• Ramlau R, Gorbunova V, Ciuleanu TE, et al. Aflibercept and Docetaxel versus Docetaxel alone after platinum failure in patients with advanced or metastatic non-small-cell lung cancer: a randomized, controlled phase III trial. J Clin Oncol 2012;30(29):3640–7
   PubMed Web of Science ®Google Scholar
• Kelly RJ, Rixe O. Axitinib - a selective inhibitor of the vascular endothelial growth factor (VEGF) receptor. Target Oncol 2009;4(4):297–305
   PubMed Web of Science ®Google Scholar
• Motzer RJ, Escudier B, Tomczak P, et al. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol 2013;14(6):552–62
   PubMed Web of Science ®Google Scholar
• Kozloff MF, Martin LP, Krzakowski M, et al. Phase I trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours. Br J Cancer 2012;107(8):1277–85
   PubMed Web of Science ®Google Scholar
• Twelves C, Chmielowska E, Havel L, et al. Randomised phase II study of axitinib or bevacizumab combined with paclitaxel/carboplatin as first-line therapy for patients with advanced non-small-cell lung cancer. Ann Oncol 2014;25(1):132–8
   PubMed Web of Science ®Google Scholar
• Belani CP, Yamamoto N, Bondarenko IM, et al. Randomized phase II study of pemetrexed/cisplatin with or without axitinib for non-squamous non-small-cell lung cancer. BMC Cancer 2014;14:290
   PubMed Web of Science ®Google Scholar
• DeRose P, Thorpe PE, Gerber DE. Development of bavituximab, a vascular targeting agent with immune-modulating properties, for lung cancer treatment. Immunotherapy 2011;3(8):933–44
   PubMed Web of Science ®Google Scholar
• Digumarti R, Bapsy PP, Suresh AV, et al. Bavituximab plus paclitaxel and carboplatin for the treatment of advanced non-small-cell lung cancer. Lung cancer 2014;86(2):231–6
   PubMed Web of Science ®Google Scholar
• Shtivelband M, Spigel DR, Gerber DE, et al. Randomized, blinded, placebo-controlled phase II trial of docetaxel and bavituximab as second-line therapy in locally advanced or metastatic non-squamous non-small cell lung cancer. ASCO Meeting Abstracts 2013;31(15 Suppl):8095
   Google Scholar
• Wong TW, Lee FY, Emanuel S, et al. Antitumor and antiangiogenic activities of BMS-690514, an inhibitor of human EGF and VEGF receptor kinase families. Clin Cancer Res 2011;17(12):4031–41
   PubMed Web of Science ®Google Scholar
• Soria JC, Baselga J, Hanna N, et al. Phase I-IIa study of BMS-690514, an EGFR, HER-2 and -4 and VEGFR-1 to -3 oral tyrosine kinase inhibitor, in patients with advanced or metastatic solid tumours. Eur J Cancer 2013;49(8):1815–24
   PubMed Web of Science ®Google Scholar
• Brave SR, Ratcliffe K, Wilson Z, et al. Assessing the activity of cediranib, a VEGFR-2/3 tyrosine kinase inhibitor, against VEGFR-1 and members of the structurally related PDGFR family. Mol Cancer Ther 2011;10(5):861–73
   PubMed Web of Science ®Google Scholar
• Goss GD, Arnold A, Shepherd FA, et al. Randomized, double-blind trial of carboplatin and paclitaxel with either daily oral cediranib or placebo in advanced non-small-cell lung cancer: NCIC clinical trials group BR24 study. J Clin Oncol 2010;28(1):49–55
   PubMed Web of Science ®Google Scholar
• Laurie SA, Solomon BJ, Seymour L, et al. Randomised, double-blind trial of carboplatin and paclitaxel with daily oral cediranib or placebo in patients with advanced non-small cell lung cancer: NCIC Clinical Trials Group study BR29. Eur J Cancer 2014;50(4):706–12
   PubMed Web of Science ®Google Scholar
• Dy GK, Mandrekar SJ, Nelson GD, et al. A randomized phase II study of gemcitabine and carboplatin with or without cediranib as first-line therapy in advanced non-small-cell lung cancer: North Central Cancer Treatment Group Study N0528. J Thorac Oncol 2013;8(1):79–88
   PubMed Web of Science ®Google Scholar
• Campbell NP, Kunnavakkam R, Leighl N, et al. Cediranib in patients with malignant mesothelioma: a phase II trial of the University of Chicago Phase II Consortium. Lung cancer 2012;78(1):76–80
   PubMed Web of Science ®Google Scholar
• Ramalingam SS, Belani CP, Mack PC, et al. Phase II study of Cediranib (AZD 2171), an inhibitor of the vascular endothelial growth factor receptor, for second-line therapy of small cell lung cancer (National Cancer Institute #7097). J Thorac Oncol 2010;5(8):1279–84
   PubMed Web of Science ®Google Scholar
• Lok W, Klein RQ, Saif MW. Aurora kinase inhibitors as anti-cancer therapy. Anticancer Drugs 2010;21(4):339–50
   PubMed Web of Science ®Google Scholar
• Cohen RB, Jones SF, Aggarwal C, et al. A phase I dose-escalation study of danusertib (PHA-739358) administered as a 24-hour infusion with and without granulocyte colony-stimulating factor in a 14-day cycle in patients with advanced solid tumors. Clin Cancer Res 2009;15(21):6694–701
   PubMed Web of Science ®Google Scholar
• Schoffski P, Besse B, Gauler T, et al. Efficacy and safety of biweekly i.v. administrations of the Aurora kinase inhibitor danusertib hydrochloride in independent cohorts of patients with advanced or metastatic breast, ovarian, colorectal, pancreatic, small-cell and non-small-cell lung cancer: a multi-tumour, multi-institutional phase II study. Ann Oncol 2015;26(3):598–607
   PubMed Web of Science ®Google Scholar
• Gauler TC, Besse B, Novello S, et al. Phase II study of danusertib (D) in advanced/metastatic non-small cell lung cancers (NSCLC). ASCO Meeting Abstracts 2013;31(15 Suppl):e19138
   Google Scholar
• Schlumberger M, Tahara M, Wirth LJ, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med 2015;372(7):621–30
   PubMed Web of Science ®Google Scholar
• Ogino H, Hanibuchi M, Kakiuchi S, et al. E7080 suppresses hematogenous multiple organ metastases of lung cancer cells with nonmutated epidermal growth factor receptor. Mol Cancer Ther 2011;10(7):1218–28
   PubMed Web of Science ®Google Scholar
• Nishio M, Horai T, Horiike A, et al. Phase 1 study of lenvatinib combined with carboplatin and paclitaxel in patients with non-small-cell lung cancer. Br J Cancer 2013;109(3):538–44
   PubMed Web of Science ®Google Scholar
• Havel L, Lee J-S, Lee KH, et al. E7080 (lenvatinib) in addition to best supportive care (BSC) versus BSC alone in third-line or greater nonsquamous, non-small cell lung cancer (NSCLC). ASCO Meeting Abstracts 2014;32(15 Suppl):8043
   Google Scholar
• Albert DH, Tapang P, Magoc TJ, et al. Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. Mol Cancer Ther 2006;5(4):995–1006
   PubMed Web of Science ®Google Scholar
• Wong CI, Koh TS, Soo R, et al. Phase I and biomarker study of ABT-869, a multiple receptor tyrosine kinase inhibitor, in patients with refractory solid malignancies. J Clin Oncol 2009;27(28):4718–26
   PubMed Web of Science ®Google Scholar
• Tan EH, Goss GD, Salgia R, et al. Phase 2 trial of Linifanib (ABT-869) in patients with advanced non-small cell lung cancer. J Thorac Oncol 2011;6(8):1418–25
   PubMed Web of Science ®Google Scholar
• Ramalingam SS, Shtivelband M, Soo RA, et al. Randomized phase II study of carboplatin and paclitaxel with either linifanib or placebo for advanced nonsquamous non-small-cell lung cancer. J Clin Oncol 2015;33(5):433–41
   PubMed Web of Science ®Google Scholar
• Bello E, Colella G, Scarlato V, et al. E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer Res 2011;71(4):1396–405
   PubMed Web of Science ®Google Scholar
• Soria JC, DeBraud F, Bahleda R, et al. Phase I/IIa study evaluating the safety, efficacy, pharmacokinetics, and pharmacodynamics of lucitanib in advanced solid tumors. Ann Oncol 2014;25(11):2244–51
   PubMed Web of Science ®Google Scholar
• Spigel DR, Cereda R, Litten JB, et al. A single arm, open-label, phase II study to assess the efficacy of lucitanib in patients with FGFR1-amplified squamous NSCLC (sqNSCLC). ASCO Meeting Abstracts 2014;32(15 Suppl):TPS8119
   Google Scholar
• Hilberg F, Roth GJ, Krssak M, et al. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res 2008;68(12):4774–82
   PubMed Web of Science ®Google Scholar
• Kutluk Cenik B, Ostapoff KT, Gerber DE, et al. BIBF 1120 (nintedanib), a triple angiokinase inhibitor, induces hypoxia but not EMT and blocks progression of preclinical models of lung and pancreatic cancer. Mol Cancer Ther 2013;12(6):992–1001
   PubMed Web of Science ®Google Scholar
• Reck M, Kaiser R, Eschbach C, et al. A phase II double-blind study to investigate efficacy and safety of two doses of the triple angiokinase inhibitor BIBF 1120 in patients with relapsed advanced non-small-cell lung cancer. Ann Oncol 2011;22(6):1374–81
   PubMed Web of Science ®Google Scholar
• Hanna NH, Kaiser R, Sullivan RN, et al. Lume-lung 2: A multicenter, randomized, double-blind, phase III study of nintedanib plus pemetrexed versus placebo plus pemetrexed in patients with advanced nonsquamous non-small cell lung cancer (NSCLC) after failure of first-line chemotherapy. ASCO Meeting Abstracts 2013;31(15 Suppl):8034
   Google Scholar
• Hori K, Saito S, Kubota K. A novel combretastatin A-4 derivative, AC7700, strongly stanches tumour blood flow and inhibits growth of tumours developing in various tissues and organs. Br J Cancer 2002;86(10):1604–14
   PubMed Web of Science ®Google Scholar
• von Pawel J, Gorbounova V, Reck M, et al. DISRUPT: a randomised phase 2 trial of ombrabulin (AVE8062) plus a taxane-platinum regimen as first-line therapy for metastatic non-small cell lung cancer. Lung cancer 2014;85(2):224–9
   PubMed Web of Science ®Google Scholar
• Sternberg CN, Davis ID, Mardiak J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 2010;28(6):1061–8
   PubMed Web of Science ®Google Scholar
• van der Graaf WT, Blay JY, Chawla SP, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2012;379(9829):1879–86
   PubMed Web of Science ®Google Scholar
• Altorki N, Lane ME, Bauer T, et al. Phase II proof-of-concept study of pazopanib monotherapy in treatment-naive patients with stage I/II resectable non-small-cell lung cancer. J Clin Oncol 2010;28(19):3131–7
   PubMed Web of Science ®Google Scholar
• Weiss JM, Villaruz LC, Socinski MA, et al. A single-arm phase II trial of pazopanib in patients with advanced non-small cell lung cancer with non-squamous histology with disease progression on bevacizumab containing therapy. Lung cancer 2014;86(2):288–90
   PubMed Web of Science ®Google Scholar
• Thomas SP, Ho T-TA, Jackson KL, et al. A phase II study of pazopanib (GW786034) in patients with stage IV non-small cell lung cancer that have failed at least two prior chemotherapy regimens. ASCO Meeting Abstracts 2014;32(15 Suppl):e19008
   Google Scholar
• Infante JR, Novello S, Ma WW, et al. Phase Ib trial of the oral angiogenesis inhibitor pazopanib administered concurrently with pemetrexed in patients with advanced solid tumors. Invest New Drugs 2013;31(4):927–36
   PubMed Web of Science ®Google Scholar
• Scagliotti GV, Felip E, Besse B, et al. An open-label, multicenter, randomized, phase II study of pazopanib in combination with pemetrexed in first-line treatment of patients with advanced-stage non-small-cell lung cancer. J Thorac Oncol 2013;8(12):1529–37
   PubMed Web of Science ®Google Scholar
• Waterhouse DM, Stults DM, Daniel DB, et al. KRAS subset analysis from randomized phase II trials of erlotinib versus erlotinib plus sorafenib or pazopanib in refractory non-small cell lung cancer (NSCLC). ASCO Meeting Abstracts 2013;31(15 Suppl):8091
   Google Scholar
• Gridelli C, Rossi A, Maione P, et al. Vascular disrupting agents: a novel mechanism of action in the battle against non-small cell lung cancer. Oncologist 2009;14(6):612–20
   PubMed Web of Science ®Google Scholar
• Singh AV, Bandi M, Raje N, et al. A novel vascular disrupting agent plinabulin triggers JNK-mediated apoptosis and inhibits angiogenesis in multiple myeloma cells. Blood 2011;117(21):5692–700
   PubMed Web of Science ®Google Scholar
• Millward M, Price T, Townsend A, et al. Phase 1 clinical trial of the novel proteasome inhibitor marizomib with the histone deacetylase inhibitor vorinostat in patients with melanoma, pancreatic and lung cancer based on in vitro assessments of the combination. Invest New Drugs 2012;30(6):2303–17
   PubMed Web of Science ®Google Scholar
• Heist RS, Aren OR, Mita AC, et al. Randomized phase 2 trial of plinabulin (NPI-2358) plus docetaxel in patients with advanced non-small cell lung cancer (NSCLC). ASCO Meeting Abstracts 2014;32(15 Suppl):8054
   Google Scholar
• Lu D, Shen J, Vil MD, et al. Tailoring in vitro selection for a picomolar affinity human antibody directed against vascular endothelial growth factor receptor 2 for enhanced neutralizing activity. J Biol Chem 2003;278(44):43496–507
   PubMed Web of Science ®Google Scholar
• Fuchs CS, Tomasek J, Yong CJ, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 2014;383(9911):31–9
   PubMed Web of Science ®Google Scholar
• Wilke H, Muro K, Van Cutsem E, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol 2014;15(11):1224–35
   PubMed Web of Science ®Google Scholar
• Clarke JM, Hurwitz HI. Targeted inhibition of VEGF receptor 2: an update on ramucirumab. Expert Opin Biol Ther 2013;13(8):1187–96
   PubMed Web of Science ®Google Scholar
• Aprile G, Rijavec E, Fontanella C, et al. Ramucirumab: preclinical research and clinical development. Onco Targets and Ther 2014;7:1997–2006
   PubMed Web of Science ®Google Scholar
• Camidge DR, Berge EM, Doebele RC, et al. A phase II, open-label study of ramucirumab in combination with paclitaxel and carboplatin as first-line therapy in patients with stage IIIB/IV non-small-cell lung cancer. J Thorac 2014;9(10):1532–9
   PubMed Web of Science ®Google Scholar
• Doebele RC, Spigel D, Tehfe M, et al. 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 2015;121(6):883–92
   PubMed Web of Science ®Google Scholar
• Mross K, Drevs J, Muller M, et al. Phase I clinical and pharmacokinetic study of PTK/ZK, a multiple VEGF receptor inhibitor, in patients with liver metastases from solid tumours. Eur J Cancer 2005;41(9):1291–9
   PubMed Web of Science ®Google Scholar
• Thomas AL, Trarbach T, Bartel C, et al. A phase IB, open-label dose-escalating study of the oral angiogenesis inhibitor PTK787/ZK 222584 (PTK/ZK), in combination with FOLFOX4 chemotherapy in patients with advanced colorectal cancer. Ann Oncol 2007;18(4):782–8
   PubMed Web of Science ®Google Scholar
• Gauler TC, Besse B, Mauguen A, et al. Phase II trial of PTK787/ZK 222584 (vatalanib) administered orally once-daily or in two divided daily doses as second-line monotherapy in relapsed or progressing patients with stage IIIB/IV non-small-cell lung cancer (NSCLC). Ann Oncol 2012;23(3):678–87
   PubMed Web of Science ®Google Scholar
• Jahan T, Gu L, Kratzke R, et al. Vatalanib in malignant mesothelioma: a phase II trial by the Cancer and Leukemia Group B (CALGB 30107). Lung Cancer 2012;76(3):393–6
   PubMed Web of Science ®Google Scholar
• Gaya A, Tse V. A preclinical and clinical review of aflibercept for the management of cancer. Cancer Treat Rev 2012;38(5):484–93
   PubMed Web of Science ®Google Scholar
• Leighl NB, Raez LE, Besse B, et al. A multicenter, phase 2 study of vascular endothelial growth factor trap (Aflibercept) in platinum- and erlotinib-resistant adenocarcinoma of the lung. J Thorac Oncol 2010;5(7):1054–9
   PubMed Web of Science ®Google Scholar
• Chen H, Modiano MR, Neal JW, et al. A phase II multicentre study of ziv-aflibercept in combination with cisplatin and pemetrexed in patients with previously untreated advanced/metastatic non-squamous non-small cell lung cancer. Br J Cancer 2014;110(3):602–8
   PubMed Web of Science ®Google Scholar
• Allen JW, Moon J, Redman M, et al. Southwest Oncology Group S0802: a randomized, phase II trial of weekly topotecan with and without ziv-aflibercept in patients with platinum-treated small-cell lung cancer. J Clin Oncol 2014;32(23):2463–70
   PubMed Web of Science ®Google Scholar
• Barlesi F, Scherpereel A, Rittmeyer A, et al. 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 2013;31(24):3004–11
   PubMed Web of Science ®Google Scholar
• Galetta D, Cinieri S, Pisconti S, et al. Cisplatin/Pemetrexed Followed by Maintenance Pemetrexed Versus Carboplatin/Paclitaxel/Bevacizumab Followed by Maintenance Bevacizumab in Advanced Nonsquamous Lung Cancer: The GOIM (Gruppo Oncologico Italia Meridionale) ERACLE Phase III Randomized Trial. Clin Lung Cancer 2014. [Epub ahead of print]
   Web of Science ®Google Scholar
• Herbst RS, Ansari R, Bustin F, et al. 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 2011;377(9780):1846–54
   PubMed Web of Science ®Google Scholar
• Johnson BE, Kabbinavar F, Fehrenbacher L, et al. 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 2013;31(31):3926–34
   PubMed Web of Science ®Google Scholar
• 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):4349–57
   PubMed Web of Science ®Google Scholar
• Reck M, von Pawel J, Zatloukal P, et al. 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 2010;21(9):1804–9
   PubMed Web of Science ®Google Scholar
• Zinner RG, Obasaju CK, Spigel DR, et al. PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients with advanced nonsquamous non-small-cell lung cancer. J Thorac Oncol 2015;10(1):134–42
   PubMed Web of Science ®Google Scholar
• Besse B, Le Moulec S, Mazieres J, et al. Bevacizumab in Patients with Nonsquamous Non-Small Cell Lung Cancer and Asymptomatic, Untreated Brain Metastases (BRAIN): A Nonrandomized, Phase II Study. Clin Cancer Res 2015;21(8):1896–903
   PubMed Web of Science ®Google Scholar
• Hattori Y, Satouchi M, Shimada T, et al. A phase 2 study of bevacizumab in combination with carboplatin and paclitaxel in patients with non-squamous non-small-cell lung cancer harboring mutations of epidermal growth factor receptor (EGFR) after failing first-line EGFR-tyrosine kinase inhibitors (HANSHIN Oncology Group 0109). Lung Cancer 2015;87(2):136–40
   PubMed Web of Science ®Google Scholar
• Kotsakis A, Kentepozidis N, Emmanouilidis C, et al. Sequential administration of vinorelbine plus cisplatin and bevacizumab followed by docetaxel plus gemcitabine and bevacizumab compared to docetaxel plus cisplatin and bevacizumab regimen as first-line therapy for advanced or metastatic non-squamous non-small cell lung cancer: A multicenter randomized phase II trial of the Hellenic Oncology Research Group (HORG). Lung Cancer 2015;88(1):57–62
   PubMed Web of Science ®Google Scholar
• Ohyanagi F, Yanagitani N, Kudo K, et al. Phase II study of docetaxel-plus-bevacizumab combination therapy in patients previously treated for advanced non-squamous non-small cell lung cancer. Anticancer Res 2014;34(9):5153–8
   PubMed Web of Science ®Google Scholar
• Petrioli R, Francini E, Fiaschi AI, et al. Switch maintenance treatment with oral vinorelbine and bevacizumab after induction chemotherapy with cisplatin, gemcitabine and bevacizumab in patients with advanced non-squamous non-small cell lung cancer: a phase II study. Med Oncol 2015;32(4):134
   PubMed Web of Science ®Google Scholar
• Takiguchi Y, Iwasawa S, Minato K, et al. Phase II study of carboplatin, docetaxel and bevacizumab for chemotherapy-naive patients with advanced non-squamous non-small cell lung cancer. Int J Clin Oncol 2014. [ Epub ahead of print]
   PubMedGoogle Scholar
• Costa C, Molina MA, Drozdowskyj A, et al. The impact of EGFR T790M mutations and BIM mRNA expression on outcome in patients with EGFR-mutant NSCLC treated with erlotinib or chemotherapy in the randomized phase III EURTAC trial. Clin Cancer Res 2014;20(7):2001–10
   PubMed Web of Science ®Google Scholar
• Naumov GN, Nilsson MB, Cascone T, et al. Combined vascular endothelial growth factor receptor and epidermal growth factor receptor (EGFR) blockade inhibits tumor growth in xenograft models of EGFR inhibitor resistance. Clin Cancer Res 2009;15(10):3484–94
   PubMed Web of Science ®Google Scholar
• Li H, Takayama K, Wang S, et al. Addition of bevacizumab enhances antitumor activity of erlotinib against non-small cell lung cancer xenografts depending on VEGF expression. Cancer Chemother Pharmacol 2014;74(6):1297–305
   PubMed Web of Science ®Google Scholar
• Rosell R. What new therapeutic targets exist for EGFR-mutant NSCLC? Lancet Oncol 2014;15(11):1184–5
   PubMed Web of Science ®Google Scholar
• Seto T, Kato T, Nishio M, et al. 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 2014;15(11):1236–44
   PubMed Web of Science ®Google Scholar
• Ichihara E, Hotta K, Nogami N, et al. 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 2015;10(3):486–91
   PubMed Web of Science ®Google Scholar
• Blumenschein GRJr, Kabbinavar F, Menon H, et al. A phase II, multicenter, open-label randomized study of motesanib or bevacizumab in combination with paclitaxel and carboplatin for advanced nonsquamous non-small-cell lung cancer. Ann Oncol 2011;22(9):2057–67
   PubMed Web of Science ®Google Scholar
• Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007;356(2):125–34
   PubMed Web of Science ®Google Scholar
• Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359(4):378–90
   PubMed Web of Science ®Google Scholar
• Brose MS, Nutting CM, Jarzab B, et al. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet 2014;384(9940):319–28
   PubMed Web of Science ®Google Scholar
• Dingemans AM, Mellema WW, Groen HJ, et al. A phase II study of sorafenib in patients with platinum-pretreated, advanced (Stage IIIb or IV) non-small cell lung cancer with a KRAS mutation. Clin Cancer Res 2013;19(3):743–51
   PubMed Web of Science ®Google Scholar
• Lind JS, Dingemans AM, Groen HJ, et al. A multicenter phase II study of erlotinib and sorafenib in chemotherapy-naive patients with advanced non-small cell lung cancer. Clin Cancer Res 2010;16(11):3078–87
   PubMed Web of Science ®Google Scholar
• Spigel DR, Burris HA, Greco FA, et al. Randomized, double-blind, placebo-controlled, phase II trial of sorafenib and erlotinib or erlotinib alone in previously treated advanced non-small-cell lung cancer. J Clin Oncol 2011;29(18):2582–9
   PubMed Web of Science ®Google Scholar
• Zhou Q, Zhou CC, Chen GY, et al. A multicenter phase II study of sorafenib monotherapy in clinically selected patients with advanced lung adenocarcinoma after failure of EGFR-TKI therapy (Chinese Thoracic Oncology Group, CTONG 0805). Lung cancer 2014;83(3):369–73
   PubMed Web of Science ®Google Scholar
• Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007;356(2):115–24
   PubMed Web of Science ®Google Scholar
• Demetri GD, van Oosterom AT, Garrett CR, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 2006;368(9544):1329–38
   PubMed Web of Science ®Google Scholar
• Raymond E, Dahan L, Raoul JL, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 2011;364(6):501–13
   PubMed Web of Science ®Google Scholar
• Scagliotti GV, Krzakowski M, Szczesna A, et al. 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 2012;30(17):2070–8
   PubMed Web of Science ®Google Scholar
• Groen HJ, Socinski MA, Grossi F, et al. A randomized, double-blind, phase II study of erlotinib with or without sunitinib for the second-line treatment of metastatic non-small-cell lung cancer (NSCLC). Ann Oncol 2013;24(9):2382–9
   PubMed Web of Science ®Google Scholar
• Heist RS, Wang X, Hodgson L, et al. CALGB 30704 (Alliance): A randomized phase II study to assess the efficacy of pemetrexed or sunitinib or pemetrexed plus sunitinib in the second-line treatment of advanced non-small-cell lung cancer. J Thorac Oncol 2014;9(2):214–21
   PubMed Web of Science ®Google Scholar
• Wells SAJr, Robinson BG, Gagel RF, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol 2012;30(2):134–41
   PubMed Web of Science ®Google Scholar
• Boer K, Lang I, Llombart-Cussac A, et al. Vandetanib with docetaxel as second-line treatment for advanced breast cancer: a double-blind, placebo-controlled, randomized Phase II study. Invest New Drugs 2012;30(2):681–7
   PubMed Web of Science ®Google Scholar
• Herbst RS, Sun Y, Eberhardt WE, et al. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. Lancet Oncol 2010;11(7):619–26
   PubMed Web of Science ®Google Scholar
• Lee JS, Hirsh V, Park K, et al. Vandetanib Versus placebo in patients with advanced non-small-cell lung cancer after prior therapy with an epidermal growth factor receptor tyrosine kinase inhibitor: a randomized, double-blind phase III trial (ZEPHYR). J Clin Oncol 2012;30(10):1114–21
   PubMed Web of Science ®Google Scholar
• Natale RB, Thongprasert S, Greco FA, et al. Phase III trial of vandetanib compared with erlotinib in patients with previously treated advanced non-small-cell lung cancer. J Clin Oncol 2011;29(8):1059–66
   PubMed Web of Science ®Google Scholar
• Ahn JS, Lee KH, Sun JM, et al. A randomized, phase II study of vandetanib maintenance for advanced or metastatic non-small-cell lung cancer following first-line platinum-doublet chemotherapy. Lung cancer 2013;82(3):455–60
   PubMed Web of Science ®Google Scholar
• Aisner J, Manola JB, Dakhil SR, et al. Vandetanib plus chemotherapy for induction followed by vandetanib or placebo as maintenance for patients with advanced non-small-cell lung cancer: a randomized phase 2 PrECOG study (PrE0501). J Thorac Oncol 2013;8(8):1075–83
   PubMed Web of Science ®Google Scholar
• Gridelli C, Novello S, Zilembo N, et al. Phase II randomized study of vandetanib plus gemcitabine or gemcitabine plus placebo as first-line treatment of advanced non-small-cell lung cancer in elderly patients. J Thorac Oncol 2014;9(5):733–7
   PubMed Web of Science ®Google Scholar