Randomized Phase II Trial of Parsatuzumab (Anti‐EGFL7) or Placebo in Combination with Carboplatin, Paclitaxel, and Bevacizumab for First‐Line Nonsquamous Non‐Small Cell Lung Cancer

Lessons Learned The lack of efficacy associated with anti‐EGFL7 combined with standard bevacizumab and chemotherapy in this phase II trial in non‐small cell lung carcinoma is consistent with the lack of benefit observed in colorectal carcinoma, highlighting the challenge of enhancing the efficacy of...

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Vydané v:	The oncologist (Dayton, Ohio) Ročník 23; číslo 6; s. 654 - e58
Hlavní autori:	von Pawel, Joachim, Spigel, David R., Ervin, Thomas, Losonczy, György, Barlesi, Fabrice, Juhász, Erzsébet, Anderson, Maria, McCall, Bruce, Wakshull, Eric, Hegde, Priti, Ye, Weilan, Chen, Daniel, Chang, Ilsung, Rhee, Ina, Reck, Martin
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States AlphaMed Press 01.06.2018
Predmet:	Clinical Trial Results
ISSN:	1083-7159, 1549-490X, 1549-490X
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Abstract	Lessons Learned The lack of efficacy associated with anti‐EGFL7 combined with standard bevacizumab and chemotherapy in this phase II trial in non‐small cell lung carcinoma is consistent with the lack of benefit observed in colorectal carcinoma, highlighting the challenge of enhancing the efficacy of VEGF inhibition in unselected populations. Future efforts with agents like anti‐EGFL7 should be guided by advances in pharmacodynamic and predictive biomarker development for antiangiogenic agents. Background Epidermal growth factor‐like domain 7 (EGFL7) is an extracellular matrix‐associated protein that is upregulated during angiogenesis and supports endothelial cell survival. This phase II trial evaluated the efficacy of the anti‐EGFL7 antibody, parsatuzumab, in combination with bevacizumab plus platinum‐based therapy for advanced or recurrent nonsquamous non‐small cell lung cancer (NS‐NSCLC). Methods Patients (n = 104) were randomized to either placebo or parsatuzumab (600 mg) in combination with bevacizumab (15 mg/kg) and carboplatin/paclitaxel, administered on day 1 of each 21‐day cycle. Carboplatin and paclitaxel were administered for up to six cycles. Bevacizumab and parsatuzumab/placebo were administered for a maximum of 24 months. Results The progression‐free survival (PFS) hazard ratio (HR) was 1.7 (95% confidence interval [CI], 1.0–2.8; p = .047). The median PFS was 6.7 months for the parsatuzumab arm versus 8.1 months for the placebo arm. The hazard ratio for overall survival (OS) was 1.1 (95% CI, 0.5–2.2; p = .847). The objective response rate (ORR) was 29% in the parsatuzumab arm and 56% in the placebo arm. Overall safety and tolerability were consistent with the established toxicity profile of bevacizumab. Conclusion There was no evidence of efficacy for the addition of parsatuzumab to the combination of bevacizumab and chemotherapy for first‐line NS‐NSCLC. 经验总结在此非小细胞肺癌II期试验中, EGFL7抗体联合贝伐单抗和化疗标准治疗缺乏疗效与在结直肠癌患者中观察到的缺乏获益的情况一致, 突出显示了在非选定人群中增强VEGF抑制效力的挑战。今后有关EGFL7抗体等药物的工作应以抗血管生成药物的药效学和预测性生物标志物开发的进展为指导。摘要背景.表皮生长因子样结构域7（EGFL7）是一种细胞外基质相关蛋白, 在血管生成过程中得以上调, 可为内皮细胞存活提供支持。该II期临床试验评价了EGFL7抗体Parsatuzumab联合贝伐单抗加含铂方案治疗晚期或复发性非鳞状细胞非小细胞肺癌（NS‐NSCLC）的疗效。方法.患者（n=104）被随机分入安慰剂组或Parsatuzumab（600 mg）联合贝伐单抗（15 mg/kg）和卡铂/紫杉醇组, 在各周期的第1天接受给药, 每一周期21天。卡铂和紫杉醇最多给药六周期。贝伐单抗和Parsatuzumab/安慰剂的最长给药时间为24个月。结果.无进展生存期（PFS）风险比（HR）为1.7[95%置信区间（CI）, 1.0–2.8；p=0.047]。Parsatuzumab组与安慰剂组的中位PFS分别为6.7个月与8.1个月。总生存期（OS）风险比为1.1（95% CI, 0.5–2.2；p=0.847）。Parsatuzumab组和安慰剂组的客观缓解率（ORR）分别为29%和56%。总体安全性和耐受性与贝伐单抗的既定毒性特征一致。结论.没有证据支持Parsatuzumab联合贝伐单抗和化疗一线疗法治疗NS‐NSCLC的疗效。
AbstractList	The lack of efficacy associated with anti-EGFL7 combined with standard bevacizumab and chemotherapy in this phase II trial in non-small cell lung carcinoma is consistent with the lack of benefit observed in colorectal carcinoma, highlighting the challenge of enhancing the efficacy of VEGF inhibition in unselected populations.Future efforts with agents like anti-EGFL7 should be guided by advances in pharmacodynamic and predictive biomarker development for antiangiogenic agents.LESSONS LEARNEDThe lack of efficacy associated with anti-EGFL7 combined with standard bevacizumab and chemotherapy in this phase II trial in non-small cell lung carcinoma is consistent with the lack of benefit observed in colorectal carcinoma, highlighting the challenge of enhancing the efficacy of VEGF inhibition in unselected populations.Future efforts with agents like anti-EGFL7 should be guided by advances in pharmacodynamic and predictive biomarker development for antiangiogenic agents.Epidermal growth factor-like domain 7 (EGFL7) is an extracellular matrix-associated protein that is upregulated during angiogenesis and supports endothelial cell survival. This phase II trial evaluated the efficacy of the anti-EGFL7 antibody, parsatuzumab, in combination with bevacizumab plus platinum-based therapy for advanced or recurrent nonsquamous non-small cell lung cancer (NS-NSCLC).BACKGROUNDEpidermal growth factor-like domain 7 (EGFL7) is an extracellular matrix-associated protein that is upregulated during angiogenesis and supports endothelial cell survival. This phase II trial evaluated the efficacy of the anti-EGFL7 antibody, parsatuzumab, in combination with bevacizumab plus platinum-based therapy for advanced or recurrent nonsquamous non-small cell lung cancer (NS-NSCLC).Patients (n = 104) were randomized to either placebo or parsatuzumab (600 mg) in combination with bevacizumab (15 mg/kg) and carboplatin/paclitaxel, administered on day 1 of each 21-day cycle. Carboplatin and paclitaxel were administered for up to six cycles. Bevacizumab and parsatuzumab/placebo were administered for a maximum of 24 months.METHODSPatients (n = 104) were randomized to either placebo or parsatuzumab (600 mg) in combination with bevacizumab (15 mg/kg) and carboplatin/paclitaxel, administered on day 1 of each 21-day cycle. Carboplatin and paclitaxel were administered for up to six cycles. Bevacizumab and parsatuzumab/placebo were administered for a maximum of 24 months.The progression-free survival (PFS) hazard ratio (HR) was 1.7 (95% confidence interval [CI], 1.0-2.8; p = .047). The median PFS was 6.7 months for the parsatuzumab arm versus 8.1 months for the placebo arm. The hazard ratio for overall survival (OS) was 1.1 (95% CI, 0.5-2.2; p = .847). The objective response rate (ORR) was 29% in the parsatuzumab arm and 56% in the placebo arm. Overall safety and tolerability were consistent with the established toxicity profile of bevacizumab.RESULTSThe progression-free survival (PFS) hazard ratio (HR) was 1.7 (95% confidence interval [CI], 1.0-2.8; p = .047). The median PFS was 6.7 months for the parsatuzumab arm versus 8.1 months for the placebo arm. The hazard ratio for overall survival (OS) was 1.1 (95% CI, 0.5-2.2; p = .847). The objective response rate (ORR) was 29% in the parsatuzumab arm and 56% in the placebo arm. Overall safety and tolerability were consistent with the established toxicity profile of bevacizumab.There was no evidence of efficacy for the addition of parsatuzumab to the combination of bevacizumab and chemotherapy for first-line NS-NSCLC.CONCLUSIONThere was no evidence of efficacy for the addition of parsatuzumab to the combination of bevacizumab and chemotherapy for first-line NS-NSCLC. The lack of efficacy associated with anti-EGFL7 combined with standard bevacizumab and chemotherapy in this phase II trial in non-small cell lung carcinoma is consistent with the lack of benefit observed in colorectal carcinoma, highlighting the challenge of enhancing the efficacy of VEGF inhibition in unselected populations.Future efforts with agents like anti-EGFL7 should be guided by advances in pharmacodynamic and predictive biomarker development for antiangiogenic agents. Epidermal growth factor-like domain 7 (EGFL7) is an extracellular matrix-associated protein that is upregulated during angiogenesis and supports endothelial cell survival. This phase II trial evaluated the efficacy of the anti-EGFL7 antibody, parsatuzumab, in combination with bevacizumab plus platinum-based therapy for advanced or recurrent nonsquamous non-small cell lung cancer (NS-NSCLC). Patients ( = 104) were randomized to either placebo or parsatuzumab (600 mg) in combination with bevacizumab (15 mg/kg) and carboplatin/paclitaxel, administered on day 1 of each 21-day cycle. Carboplatin and paclitaxel were administered for up to six cycles. Bevacizumab and parsatuzumab/placebo were administered for a maximum of 24 months. The progression-free survival (PFS) hazard ratio (HR) was 1.7 (95% confidence interval [CI], 1.0-2.8; = .047). The median PFS was 6.7 months for the parsatuzumab arm versus 8.1 months for the placebo arm. The hazard ratio for overall survival (OS) was 1.1 (95% CI, 0.5-2.2; = .847). The objective response rate (ORR) was 29% in the parsatuzumab arm and 56% in the placebo arm. Overall safety and tolerability were consistent with the established toxicity profile of bevacizumab. There was no evidence of efficacy for the addition of parsatuzumab to the combination of bevacizumab and chemotherapy for first-line NS-NSCLC. Lessons Learned The lack of efficacy associated with anti‐EGFL7 combined with standard bevacizumab and chemotherapy in this phase II trial in non‐small cell lung carcinoma is consistent with the lack of benefit observed in colorectal carcinoma, highlighting the challenge of enhancing the efficacy of VEGF inhibition in unselected populations. Future efforts with agents like anti‐EGFL7 should be guided by advances in pharmacodynamic and predictive biomarker development for antiangiogenic agents. Background Epidermal growth factor‐like domain 7 (EGFL7) is an extracellular matrix‐associated protein that is upregulated during angiogenesis and supports endothelial cell survival. This phase II trial evaluated the efficacy of the anti‐EGFL7 antibody, parsatuzumab, in combination with bevacizumab plus platinum‐based therapy for advanced or recurrent nonsquamous non‐small cell lung cancer (NS‐NSCLC). Methods Patients (n = 104) were randomized to either placebo or parsatuzumab (600 mg) in combination with bevacizumab (15 mg/kg) and carboplatin/paclitaxel, administered on day 1 of each 21‐day cycle. Carboplatin and paclitaxel were administered for up to six cycles. Bevacizumab and parsatuzumab/placebo were administered for a maximum of 24 months. Results The progression‐free survival (PFS) hazard ratio (HR) was 1.7 (95% confidence interval [CI], 1.0–2.8; p = .047). The median PFS was 6.7 months for the parsatuzumab arm versus 8.1 months for the placebo arm. The hazard ratio for overall survival (OS) was 1.1 (95% CI, 0.5–2.2; p = .847). The objective response rate (ORR) was 29% in the parsatuzumab arm and 56% in the placebo arm. Overall safety and tolerability were consistent with the established toxicity profile of bevacizumab. Conclusion There was no evidence of efficacy for the addition of parsatuzumab to the combination of bevacizumab and chemotherapy for first‐line NS‐NSCLC. 经验总结在此非小细胞肺癌II期试验中, EGFL7抗体联合贝伐单抗和化疗标准治疗缺乏疗效与在结直肠癌患者中观察到的缺乏获益的情况一致, 突出显示了在非选定人群中增强VEGF抑制效力的挑战。今后有关EGFL7抗体等药物的工作应以抗血管生成药物的药效学和预测性生物标志物开发的进展为指导。摘要背景.表皮生长因子样结构域7（EGFL7）是一种细胞外基质相关蛋白, 在血管生成过程中得以上调, 可为内皮细胞存活提供支持。该II期临床试验评价了EGFL7抗体Parsatuzumab联合贝伐单抗加含铂方案治疗晚期或复发性非鳞状细胞非小细胞肺癌（NS‐NSCLC）的疗效。方法.患者（n=104）被随机分入安慰剂组或Parsatuzumab（600 mg）联合贝伐单抗（15 mg/kg）和卡铂/紫杉醇组, 在各周期的第1天接受给药, 每一周期21天。卡铂和紫杉醇最多给药六周期。贝伐单抗和Parsatuzumab/安慰剂的最长给药时间为24个月。结果.无进展生存期（PFS）风险比（HR）为1.7[95%置信区间（CI）, 1.0–2.8；p=0.047]。Parsatuzumab组与安慰剂组的中位PFS分别为6.7个月与8.1个月。总生存期（OS）风险比为1.1（95% CI, 0.5–2.2；p=0.847）。Parsatuzumab组和安慰剂组的客观缓解率（ORR）分别为29%和56%。总体安全性和耐受性与贝伐单抗的既定毒性特征一致。结论.没有证据支持Parsatuzumab联合贝伐单抗和化疗一线疗法治疗NS‐NSCLC的疗效。
Author	Rhee, Ina Hegde, Priti Reck, Martin Ye, Weilan Spigel, David R. von Pawel, Joachim Wakshull, Eric Chang, Ilsung Barlesi, Fabrice McCall, Bruce Anderson, Maria Chen, Daniel Losonczy, György Ervin, Thomas Juhász, Erzsébet
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Cites_doi	10.1242/dev.002576 10.1634/theoncologist.2016-0133 10.1016/S0002-9440(10)63273-7 10.1172/JCI24612 10.2174/092986706777585059 10.1172/JCI67892 10.1038/nm988 10.1158/0008-5472.CAN-03-3986 10.1016/j.gde.2004.12.005 10.1002/dvdy.20063 10.1200/JCO.2012.47.9626 10.1016/S0002-9440(10)62972-0 10.1097/CCO.0000000000000166 10.1200/JCO.2007.14.5466 10.1159/000314980 10.1158/1538-7445.AM2011-3295 10.1093/biomet/68.1.316 10.1056/NEJMoa061884 10.1182/blood-2011-10-322446 10.1097/JTO.0000000000000160 10.1200/jco.2011.29.15_suppl.2514 10.1152/ajplung.00178.2007 10.1038/nature02416 10.1093/emboj/cdg549
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References	2004; 10 2007; 134 2004; 165 2004; 230 2015; 27 2010; 79 2006; 13 2005; 167 2017; 22 2011; 71 2013; 31 2013; 123 1981; 68 2005; 65 2004; 428 2006; 116 2005; 15 2014; 9 2011; 29 2009; 27 2008; 294 2012; 119 2003; 22 2006; 355 Fitch (2021122510534065600_onco12377-bib-0014) 2004; 230 Patel (2021122510534065600_onco12377-bib-0022) 2013; 31 Reinmuth (2021122510534065600_onco12377-bib-0006) 2015; 27 Johnson (2021122510534065600_onco12377-bib-0002) 2013; 123 Parker (2021122510534065600_onco12377-bib-0001) 2004; 428 Garcia-Carbonero (2021122510534065600_onco12377-bib-0004) 2017; 22 Inai (2021122510534065600_onco12377-bib-0018) 2004; 165 Vosseler (2021122510534065600_onco12377-bib-0020) 2005; 65 Willett (2021122510534065600_onco12377-bib-0010) 2004; 10 Yeung (2021122510534065600_onco12377-bib-0017) 2011; 71 Mok (2021122510534065600_onco12377-bib-0024) 2014; 9 Nichol (2021122510534065600_onco12377-bib-0015) 2012; 119 Reck (2021122510534065600_onco12377-bib-0008) 2009; 27 Baluk (2021122510534065600_onco12377-bib-0021) 2005; 15 Mancuso (2021122510534065600_onco12377-bib-0019) 2006; 116 Naumovski (2021122510534065600_onco12377-bib-0003) 2011; 29 Sandler (2021122510534065600_onco12377-bib-0007) 2006; 355 Soncin (2021122510534065600_onco12377-bib-0013) 2003; 22 Campagnolo (2021122510534065600_onco12377-bib-0016) 2005; 167 Ranieri (2021122510534065600_onco12377-bib-0009) 2006; 13 Schmidt (2021122510534065600_onco12377-bib-0011) 2007; 134 Xu (2021122510534065600_onco12377-bib-0012) 2008; 294 Schoenfeld (2021122510534065600_onco12377-bib-0005) 1981; 68 Hapani (2021122510534065600_onco12377-bib-0023) 2010; 79
References_xml	– volume: 294 start-page: L17 year: 2008 end-page: L23 article-title: Epidermal growth factor‐like domain 7 protects endothelial cells from hyperoxia‐induced cell death publication-title: Am J Physiol Lung Cell Mol Physiol – volume: 15 start-page: 102 year: 2005 end-page: 111 article-title: Cellular abnormalities of blood vessels as targets in cancer publication-title: Curr Opin Genet Dev – volume: 123 start-page: 3997 year: 2013 end-page: 4009 article-title: Anti‐EGFL7 antibodies enhance stress‐induced endothelial cell death and anti‐VEGF efficacy publication-title: J Clin Invest – volume: 68 start-page: 316 year: 1981 end-page: 319 article-title: The asymptotic properties of nonparametric tests for comparing survival distributions publication-title: Biometrika – volume: 428 start-page: 754 year: 2004 end-page: 758 article-title: The endothelial‐cell‐derived secreted factor EGFL7 regulates vascular tube formation publication-title: Nature – volume: 9 start-page: 848 year: 2014 end-page: 855 article-title: 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) publication-title: J Thorac Oncol – volume: 29 start-page: 2514a issue: suppl 15 year: 2011 article-title: A phase 1b dose‐escalation study of the safety, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of the humanized monoclonal antibody (huMab) anti‐EGFL7 (MEGF0444A) in combination with bevacizumab with or without paclitaxel in patients with advanced solid tumors publication-title: J Clin Oncol – volume: 165 start-page: 35 year: 2004 end-page: 52 article-title: Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts publication-title: Am J Pathol – volume: 230 start-page: 316 year: 2004 end-page: 324 article-title: Egfl7, a novel epidermal growth factor‐domain gene expressed in endothelial cells publication-title: Dev Dyn – volume: 13 start-page: 1845 year: 2006 end-page: 1857 article-title: Vascular endothelial growth factor (VEGF) as a target of bevacizumab in cancer: From the biology to the clinic publication-title: Curr Med Chem – volume: 167 start-page: 275 year: 2005 end-page: 284 article-title: EGFL7 is a chemoattractant for endothelial cells and is up‐regulated in angiogenesis and arterial injury publication-title: Am J Pathol – volume: 31 start-page: 4349 year: 2013 end-page: 4357 article-title: 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 publication-title: J Clin Oncol – volume: 355 start-page: 2542 year: 2006 end-page: 2550 article-title: Paclitaxel–carboplatin alone or with bevacizumab for non–small‐cell lung cancer publication-title: N Engl J Med – volume: 65 start-page: 1294 year: 2005 end-page: 1305 article-title: Angiogenesis inhibition by vascular endothelial growth factor receptor‐2 blockade reduces stromal matrix metalloproteinase expression, normalizes stromal tissue, and reverts epithelial tumor phenotype in surface heterotransplants publication-title: Cancer Res – volume: 27 start-page: 1227 year: 2009 end-page: 1234 article-title: Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first‐line therapy for nonsquamous non‐small‐cell lung cancer: AVAil publication-title: J Clin Oncol – volume: 119 start-page: 1345 year: 2012 end-page: 1352 article-title: EGFL7: A unique angiogenic signaling factor in vascular development and disease publication-title: Blood – volume: 22 start-page: 375 year: 2017 end-page: e30 article-title: Randomized phase II trial of parsatuzumab (anti‐EGFL7) or placebo in combination with FOLFOX and bevacizumab for first‐line metastatic colorectal cancer publication-title: The Oncologist – volume: 71 start-page: 3295a year: 2011 article-title: Abstract 3295: Inhibiting vascular morphogenesis in tumors: EGFL7 as a novel therapeutic target publication-title: Cancer Research – volume: 10 start-page: 145 year: 2004 end-page: 147 article-title: Direct evidence that the VEGF‐specific antibody bevacizumab has antivascular effects in human rectal cancer publication-title: Nat Med – volume: 134 start-page: 2913 year: 2007 end-page: 2923 article-title: EGFL7 regulates the collective migration of endothelial cells by restricting their spatial distribution publication-title: Development – volume: 116 start-page: 2610 year: 2006 end-page: 2621 article-title: Rapid vascular regrowth in tumors after reversal of VEGF inhibition publication-title: J Clin Invest – volume: 22 start-page: 5700 year: 2003 end-page: 5711 article-title: VE‐statin, an endothelial repressor of smooth muscle cell migration publication-title: EMBO J – volume: 79 start-page: 27 year: 2010 end-page: 38 article-title: Increased risk of serious hemorrhage with bevacizumab in cancer patients: A meta‐analysis publication-title: Oncology – volume: 27 start-page: 79 year: 2015 end-page: 86 article-title: Novel angiogenesis inhibitors in nonsmall cell lung cancer publication-title: Curr Opin Oncol – volume: 134 start-page: 2913 year: 2007 ident: 2021122510534065600_onco12377-bib-0011 article-title: EGFL7 regulates the collective migration of endothelial cells by restricting their spatial distribution publication-title: Development doi: 10.1242/dev.002576 – volume: 22 start-page: 375 year: 2017 ident: 2021122510534065600_onco12377-bib-0004 article-title: Randomized phase II trial of parsatuzumab (anti-EGFL7) or placebo in combination with FOLFOX and bevacizumab for first-line metastatic colorectal cancer publication-title: The Oncologist doi: 10.1634/theoncologist.2016-0133 – volume: 165 start-page: 35 year: 2004 ident: 2021122510534065600_onco12377-bib-0018 article-title: Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts publication-title: Am J Pathol doi: 10.1016/S0002-9440(10)63273-7 – volume: 116 start-page: 2610 year: 2006 ident: 2021122510534065600_onco12377-bib-0019 article-title: Rapid vascular regrowth in tumors after reversal of VEGF inhibition publication-title: J Clin Invest doi: 10.1172/JCI24612 – volume: 13 start-page: 1845 year: 2006 ident: 2021122510534065600_onco12377-bib-0009 article-title: Vascular endothelial growth factor (VEGF) as a target of bevacizumab in cancer: From the biology to the clinic publication-title: Curr Med Chem doi: 10.2174/092986706777585059 – volume: 123 start-page: 3997 year: 2013 ident: 2021122510534065600_onco12377-bib-0002 article-title: Anti-EGFL7 antibodies enhance stress-induced endothelial cell death and anti-VEGF efficacy publication-title: J Clin Invest doi: 10.1172/JCI67892 – volume: 10 start-page: 145 year: 2004 ident: 2021122510534065600_onco12377-bib-0010 article-title: Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer publication-title: Nat Med doi: 10.1038/nm988 – volume: 65 start-page: 1294 year: 2005 ident: 2021122510534065600_onco12377-bib-0020 article-title: Angiogenesis inhibition by vascular endothelial growth factor receptor-2 blockade reduces stromal matrix metalloproteinase expression, normalizes stromal tissue, and reverts epithelial tumor phenotype in surface heterotransplants publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-03-3986 – volume: 15 start-page: 102 year: 2005 ident: 2021122510534065600_onco12377-bib-0021 article-title: Cellular abnormalities of blood vessels as targets in cancer publication-title: Curr Opin Genet Dev doi: 10.1016/j.gde.2004.12.005 – volume: 230 start-page: 316 year: 2004 ident: 2021122510534065600_onco12377-bib-0014 article-title: Egfl7, a novel epidermal growth factor-domain gene expressed in endothelial cells publication-title: Dev Dyn doi: 10.1002/dvdy.20063 – volume: 31 start-page: 4349 year: 2013 ident: 2021122510534065600_onco12377-bib-0022 article-title: 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 publication-title: J Clin Oncol doi: 10.1200/JCO.2012.47.9626 – volume: 167 start-page: 275 year: 2005 ident: 2021122510534065600_onco12377-bib-0016 article-title: EGFL7 is a chemoattractant for endothelial cells and is up-regulated in angiogenesis and arterial injury publication-title: Am J Pathol doi: 10.1016/S0002-9440(10)62972-0 – volume: 27 start-page: 79 year: 2015 ident: 2021122510534065600_onco12377-bib-0006 article-title: Novel angiogenesis inhibitors in nonsmall cell lung cancer publication-title: Curr Opin Oncol doi: 10.1097/CCO.0000000000000166 – volume: 27 start-page: 1227 year: 2009 ident: 2021122510534065600_onco12377-bib-0008 article-title: Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil publication-title: J Clin Oncol doi: 10.1200/JCO.2007.14.5466 – volume: 79 start-page: 27 year: 2010 ident: 2021122510534065600_onco12377-bib-0023 article-title: Increased risk of serious hemorrhage with bevacizumab in cancer patients: A meta-analysis publication-title: Oncology doi: 10.1159/000314980 – volume: 71 start-page: 3295a year: 2011 ident: 2021122510534065600_onco12377-bib-0017 article-title: Abstract 3295: Inhibiting vascular morphogenesis in tumors: EGFL7 as a novel therapeutic target publication-title: Cancer Research doi: 10.1158/1538-7445.AM2011-3295 – volume: 68 start-page: 316 year: 1981 ident: 2021122510534065600_onco12377-bib-0005 article-title: The asymptotic properties of nonparametric tests for comparing survival distributions publication-title: Biometrika doi: 10.1093/biomet/68.1.316 – volume: 355 start-page: 2542 year: 2006 ident: 2021122510534065600_onco12377-bib-0007 article-title: Paclitaxel–carboplatin alone or with bevacizumab for non–small-cell lung cancer publication-title: N Engl J Med doi: 10.1056/NEJMoa061884 – volume: 119 start-page: 1345 year: 2012 ident: 2021122510534065600_onco12377-bib-0015 article-title: EGFL7: A unique angiogenic signaling factor in vascular development and disease publication-title: Blood doi: 10.1182/blood-2011-10-322446 – volume: 9 start-page: 848 year: 2014 ident: 2021122510534065600_onco12377-bib-0024 article-title: 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) publication-title: J Thorac Oncol doi: 10.1097/JTO.0000000000000160 – volume: 29 start-page: 2514a issue: suppl 15 year: 2011 ident: 2021122510534065600_onco12377-bib-0003 article-title: A phase 1b dose-escalation study of the safety, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of the humanized monoclonal antibody (huMab) anti-EGFL7 (MEGF0444A) in combination with bevacizumab with or without paclitaxel in patients with advanced solid tumors publication-title: J Clin Oncol doi: 10.1200/jco.2011.29.15_suppl.2514 – volume: 294 start-page: L17 year: 2008 ident: 2021122510534065600_onco12377-bib-0012 article-title: Epidermal growth factor-like domain 7 protects endothelial cells from hyperoxia-induced cell death publication-title: Am J Physiol Lung Cell Mol Physiol doi: 10.1152/ajplung.00178.2007 – volume: 428 start-page: 754 year: 2004 ident: 2021122510534065600_onco12377-bib-0001 article-title: The endothelial-cell-derived secreted factor EGFL7 regulates vascular tube formation publication-title: Nature doi: 10.1038/nature02416 – volume: 22 start-page: 5700 year: 2003 ident: 2021122510534065600_onco12377-bib-0013 article-title: VE-statin, an endothelial repressor of smooth muscle cell migration publication-title: EMBO J doi: 10.1093/emboj/cdg549
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Snippet	Lessons Learned The lack of efficacy associated with anti‐EGFL7 combined with standard bevacizumab and chemotherapy in this phase II trial in non‐small cell... The lack of efficacy associated with anti-EGFL7 combined with standard bevacizumab and chemotherapy in this phase II trial in non-small cell lung carcinoma is...
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Title	Randomized Phase II Trial of Parsatuzumab (Anti‐EGFL7) or Placebo in Combination with Carboplatin, Paclitaxel, and Bevacizumab for First‐Line Nonsquamous Non‐Small Cell Lung Cancer
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