Antiangiogenic Agents in Combination with Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer

Figures & data

Table 1 . Results from phase II and III trials of bevacizumab in combination with chemotherapy as first-line or second-line NSCLC treatment

Reference	Phase	Regimen	N^a	RR (%)	PFS (mo)	OS (mo)
First-line
Johnson 2004 ^[Citation21]	II	CBDCA AUC 6 + PTX 200 mg/m^2	32	18.8	TTP, 4.2	14.9
		CBDCA + PTX + Bev 7.5 mg/kg	32	28.1	TTP, 4.3	11.6
		CBDCA + PTX + Bev 15 mg/kg	35	31.5	TTP, 7.4	17.7
Patel 2009 ^[Citation22]	II	CBDCA AUC 6 + Pem 500 mg/m^2 + Bev 15 mg/kg with maintenance Pem 500 mg/m^2 + Bev 15 mg/kg	49	55	7.8	14.1
Skaff 2009 ^[Citation23]	II	CBDCA AUC 6 + Pem 500 mg/m^2 + Bev 15 mg/kg	25	36	TTP, 7.25	ND
Dalsania 2007 ^[Citation24]	II	CBDCA AUC 6 + Pem 500 mg/m^2 + Bev 15 mg/kg	12	60	ND	ND
Waples 2008 ^[Citation25]	II	OX 120 mg/m^2 + Pem 500 mg/m^2 + Bev 15 mg/kg	58	26	7.8	16.7
Wozniak 2009 ^[Citation26]	II	Pem 500 mg/m^2 + Gem 1500 mg/m^2 + Bev 10 mg/kg every 2 weeks	18	61	ND	ND
Lilenbaum 2008 ^[Citation27]	II	OX 130 mg/m^2 + Gem 1,000 mg/m^2 + Bev 15 mg/kg	44	43	ND	13.7
Leon 2009 ^[Citation28]	II	CDDP 80 mg/m^2 + Vinorelbine 25 mg/m^2 + Bev 15 mg/kg	17	29.4	4.6	ND
Herbst 2007 ^[Citation29]	II	TXT 75 mg/m^2 or Pem 500 mg/m^2 + Bev 15 mg/kg	40	12.5	4.8	12.6
		TXT 75 mg/m^2 or Pem 500 mg/m^2 + placebo	41	12.2	3.0	8.6
		Bev 15 mg/kg + Erlotinib 150 mg/day	39	17.9	4.4	13.7
Ferrer 2009 ^[Citation30]	II	CDDP 75 mg/m^2 + TXT 75 mg/m^2 + Bev 15 mg/kg	46	63	7.8	13.5
William 2010 ^[Citation30]	II	CBDCA AUC 6 + TXT 75 mg/m^2 + Bev 15 mg/kg	40	52.5	7.9	16.5
Reynolds 2009 ^[Citation31]	II	nabPTX 300 mg/m^2 CBDCA AUC 6 + Bev 15 mg/kg	50	31	9.8	16.8
Clement-Duchene 2010 ^[Citation32]	II	CBDCA AUC 5 + Gem 1000 mg/m^2 + Bev 15 mg/kg	47	14.9	8.7	12.8
Sandler 2006 ^[Citation20]	III	CBDCA AUC 6 + PTX 200 mg/m^2	433	15	4.5	10.3
		CBDCA + PTX + Bev 15 mg/kg	417	35	6.2	12.3
Reck 2009 ^[Citation33]	III	CDDP 80 mg/m^2 + Gem 1,250 mg/m^2	327	20.1	6.1	NR
		CDDP + Gem + Bev 7.5 mg/kg	330	34.1	6.7	NR
		CDDP + Gem + Bev 15 mg/kg	329	30.4	6.5	NR
Crino 2010 ^[Citation34]	III	Chemotherapy + Bev 7.5 or 15 mg/kg	2,212	51.0	TTP, 7.8	14.6
Fischbach 2009 ^[Citation35]	III	Chemotherapy + Bev 7.5 or 15 mg/kg	1,758	ND	6.7	ND
Second-line
Adjei 2010 ^[Citation36]	II	Pem 500 mg/m^2 + Bev 15 mg/kg	48	10	4.0	8.6
Heist 2008 ^[Citation37]	II	Pem 500 mg/m^2 + OX 120 mg/m^2 + Bev 15 mg/kg	34	27	5.8	12.5

^aPatients evaluable for efficacy.

Abbreviations. AUC: area under the curve; Bev: bevacizumab; CBDCA: carboplatin; CDDP: cisplatin, EFS: event-free survival; Gem: gemcitabine; ND: no data available; NSCLC: non-small cell lung cancer; OS: overall survival; OX: oxaliplatin; Pem: pemetrexed; PFS: progression-free survival; PTX: paclitaxel; RR: response rate; TTP: time to progression; TXT: docetaxel.

Table 2 . Overview of ongoing (actively recruiting) phase II and III trials of bevacizumab in NSCLC^a

Phase	Trial description	Identifier number
Early-stage NSCLC
II	Neoadjuvant bevacizumab in combination with cisplatin-based chemotherapy versus neoadjuvant cisplatin and docetaxel, both followed by adjuvant bevacizumab, in patients with Stage IB–IIIA NSCLC undergoing surgical resection.	NCT00130780
II	Neoadjuvant bevacizumab in combination with carboplatin and paclitaxel in patients with Stage IB−IIA NSCLC undergoing surgical resection.	NCT00960297
II	Neoadjuvant bevacizumab in combination with cisplatin and gemcitabine, followed by cisplatin and etoposide after surgical resection, in patients with Stage IIIA NSCLC.	NCT00924209
II	Adjuvant bevacizumab in combination with carboplatin and docetaxel, followed by maintenance bevacizumab and erlotinib, in patients with surgically resected Stage IB−IIIA NSCLC.	NCT00621049
III	Adjuvant bevacizumab in combination with chemotherapy versus chemotherapy alone in patients with surgically resected Stage IB−IIIA NSCLC.	NCT00324805
First-line in advanced NSCLC
II	Bevacizumab in combination with carboplatin and gemcitabine.	NCT00150657
II	Bevacizumab in combination with carboplatin and gemcitabine.	NCT00400803
II	Bevacizumab in combination with carboplatin and abraxane.	NCT00642759
II	Bevacizumab in combination with carboplatin, paclitaxel, and erlotinib.	NCT00550537
II	Bevacizumab in combination with carboplatin, paclitaxel, and imprime PGG® injection.	NCT00874107
II	Bevacizumab in combination with paclitaxel and gemcitabine.	NCT00655850
II	Bevacizumab in combination with docetaxel in patients aged >75 years.	NCT00541099
II	Bevacizumab in combination with gemcitabine and cisplatin versus bevacizumab in combination with gemcitabine in patients aged ≥70 years.	NCT01077713
II	Bevacizumab in combination with platinum-based chemotherapy versus bevacizumab in combination with erlotinib.	NCT00531960
II	Bevacizumab in combination with carboplatin and paclitaxel versus bevacizumab in combination with carboplatin, paclitaxel, and erlotinib in nonsmokers.	NCT00976677
II	Bevacizumab in combination with carboplatin and paclitaxel versus bevacizumab in combination with carboplatin, paclitaxel, and cixutumumab.	NCT00955305
II	Bevacizumab in combination with carboplatin and paclitaxel, versus CT-322 in combination with carboplatin and paclitaxel.	NCT00850577
II	Bevacizumab in combination with carboplatin and paclitaxel, or second-line bevacizumab in combination with erlotinib, in patients with asymptomatic untreated brain metastases.	NCT00800202
II	Bevacizumab in combination with pemetrexed.	NCT00254319
II	Bevacizumab in combination with paclitaxel and pemetrexed.	NCT00807573
II	Bevacizumab in combination with carboplatin and pemetrexed.	NCT00614822
II	Bevacizumab in combination with carboplatin and pemetrexed in patients with ECOG performance status 2.	NCT00892710
II	Bevacizumab in combination with cisplatin and pemetrexed.	NCT00998166
II	Bevacizumab in combination with gemcitabine and pemetrexed.	NCT00438204
II	Bevacizumab in combination with erlotinib in patients aged ≥70 years.	NCT00553800
II	Bevacizumab in combination with cisplatin and pemetrexed versus bevacizumab in combination with erlotinib.	NCT01116219
II	Bevacizumab in combination with cisplatin and pemetrexed, followed by maintenance bevacizumab and pemetrexed.	NCT01004250
II	Bevacizumab in combination with carboplatin and gemcitabine, followed by bevacizumab in combination with erlotinib at disease progression.	NCT00702975
II	Bevacizumab in combination with carboplatin and docetaxel, followed by second-line bevacizumab and pemetrexed or second-line pemetrexed alone.	NCT00766246
III	Carboplatin and paclitaxel with or without bevacizumab versus carboplatin, paclitaxel, and cetuximab with or without bevacizumab.	NCT00946712
III	Bevacizumab in combination with pemetrexed, versus bevacizumab alone and pemetrexed alone.	NCT01107626
III	Bevacizumab in combination with pemetrexed and carboplatin versus bevacizumab in combination with pemetrexed in patients aged >65 years.	NCT00976456
III	Bevacizumab in combination with cisplatin and pemetrexed, followed by maintenance bevacizumab and pemetrexed, versus maintenance bevacizumab alone.	NCT00961415
III	Bevacizumab in combination with carboplatin and pemetrexed, followed by maintenance bevacizumab and pemetrexed, versus first-line bevacizumab in combination with carboplatin and paclitaxel, followed by maintenance bevacizumab.	NCT00762034
III	Bevacizumab in combination with carboplatin and paclitaxel, followed by maintenance bevacizumab, versus first-line pemetrexed in combination with carboplatin, followed by maintenance pemetrexed.	NCT00948675
Second- or third-line in advanced NSCLC
II	Second- or third-line bevacizumab in combination with carboplatin and paclitaxel.	NCT00753909
II	Second-line bevacizumab in combination with vinorelbine.	NCT00755170
II	Second-line bevacizumab in combination with docetaxel.	NCT00741195
II	Second-line bevacizumab in combination with pemetrexed.	NCT00741221
II	Second-line bevacizumab in combination with pemetrexed versus pemetrexed alone.	NCT00735891
II	Second-line bevacizumab in combination with erlotinib.	NCT00749567
II	Second-line bevacizumab in combination with erlotinib.	NCT00436332
II	Second-line bevacizumab in combination with ixabepilone.	NCT01057212

^aClinicalTrials.gov accessed on November 22, 2010.

Abbreviations. ECOG: Eastern Cooperative Oncology Group; NSCLC: non-small cell lung cancer.

Table 3 . Results from phase II and III trials of antiangiogenic TKIs in combination with chemotherapy in NSCLC

Reference	Phase	Regimen	N^a	RR (%)	PFS (mo)	OS (mo)
Sorafenib
Flaherty 2008 (66)	I	CBDCA AUC 6 + PTX 225 mg/m^2 + sorafenib 100, 200, or 400 mg twice daily.	39	26	10.1 (melanoma)	NR
					3.4 (other tumor types)
Scagliotti 2010 (67)	III	CBDCA AUC 6 + PTX 225 mg/m^2 + placebo.	462	24	5.4	10.6
		CBDCA AUC 6 + PTX 225 mg/m^2 + sorafenib 400 mg twice daily.	464	27.4	4.6	10.7
Cediranib
Gadgeel 2009 (68)	II	Pem 500 mg/m^2 + cediranib 30 mg/day.	31	16	NR	NR
Vandetanib
De Boer 2009 (69)	I	Pem 500 mg/m^2 + vandetanib 100 mg/day.	10	10	NR	NR
		Pem 500 mg/m^2 + vandetanib 300 mg/day.	11	0	NR	NR
Heymach 2008 (70)	II	CBDCA AUC 6 + PTX 200 mg/m^2 + placebo.	52	25	∼6 (23 weeks)	12.6
		CBDCA AUC 6 + PTX 200 mg/m^2 + vandetanib 300 mg/day.	56	32	∼6 (24 weeks)	10.2
Heymach 2007 (71)	II	TXT 75 mg/m^2 + placebo.	41	12	2.8	13.4
		TXT 75 mg/m^2 + vandetanib 100 mg/day.	42	26	4.3	13.1
		TXT 75 mg/m^2 + vandetanib 300 mg/day.	44	18	4.0	7.9
Herbst 2010 (72)	III	TXT 75 mg/m^2 + placebo.	697	10	3.2	9.9
		TXT 75 mg/m^2 + vandetanib 100 mg/day.	694	17	4.0	10.3
De Boer 2009 (73)	III	Pem 500 mg/m^2 + placebo.	278	7.9	NR	NR
		Pem 500 mg/m^2 + vandetanib 100 mg/day.	256	19.1	NR	NR

^aPatients evaluable for efficacy.

Abbreviations. AUC: area under the curve; CBDCA: carboplatin; NR: not reported; NSCLC: non-small cell lung cancer; OS: overall survival; Pem: pemetrexed; PFS: progression-free survival; PTX: paclitaxel; RR: response rate; TKI: tyrosine kinase inhibitor; TXT: docetaxel.

Table 4 . Overview of ongoing (actively recruiting) phase II and III trials of antiangiogenic TKIs in NSCLC^a

Agent	Trial Description	Identifier Number
Sorafenib
	Phase II trial of sorafenib in patients with advanced NSCLC after failure of EGFR-TKI.	NCT00922584
	Phase II trial of sorafenib in combination with erlotinib in patients with advanced NSCLC after failure of chemotherapy.	NCT00801385
	Phase II trial of sorafenib in patients with relapsed or refractory advanced NSCLC (nonsmokers or former light smokers).	NCT00754923
	Phase III trial of third- or fourth-line sorafenib versus placebo in patients with predominantly nonsquamous NSCLC.	NCT00863746
Sunitinib
	Phase II trial of first-line sunitinib in patients aged >70 years with advanced NSCLC.	NCT00864721
	Phase II trial of second-line sunitinib and/or pemetrexed in patients with advanced NSCLC.	NCT00698815
	Phase II trial of sunitinib in combination with cisplatin and docetaxel as salvage therapy in patients with advanced NSCLC.	NCT01019798
	Phase II trial of sunitinib as maintenance therapy in patients with advanced NSCLC previously treated with combination chemotherapy.	NCT01210053
	Phase III trial of sunitinib versus placebo as maintenance therapy in patients with advanced NSCLC previously treated with combination chemotherapy.	NCT00693992
Cediranib
	Phase III trial of first-line cediranib in combination with carboplatin and paclitaxel in patients with advanced NSCLC (BR. 29).	NCT00795340
	Phase II trial of second- or third-line cediranib in combination with pemetrexed in patients with advanced NSCLC.	NCT00410904
Vandetanib
	Phase II trial of first-line vandetanib in combination with carboplatin and paclitaxel in patients with advanced NSCLC.	NCT00093392
BIBF 1120
	Phase III trial of second-line BIBF 1120 in combination with docetaxel versus docetaxel alone in patients with advanced NSCLC (LUME-Lung 1).	NCT00805194
	Phase III trial of second-line BIBF 1120 in combination with pemetrexed versus pemetrexed alone in patients with advanced nonsquamous NSCLC (LUME-Lung 2).	NCT00806819
Pazopanib
	Phase II/III trial of adjuvant pazopanib versus placebo in patients with stage I surgically resected NSCLC.	NCT00775307
	Phase II trial of first-line pazopanib in combination with paclitaxel versus carboplatin in combination with paclitaxel in patients with advanced NSCLC.	NCT00866528
	Phase II trial of second-line pazopanib in combination with erlotinib versus erlotinib alone in patients with advanced NSCLC.	NCT01027598
	Phase II trial of third-line pazopanib in patients with advanced NSCLC.	NCT01049776
Axitinib
	Phase II trial of first-line axitinib in combination with cisplatin and gemcitabine in patients with squamous NSCLC.	NCT00735904

^aClinicalTrials.gov accessed on November 22, 2010.

Abbreviations. EGFR: epidermal growth factor receptor; NSCLC: non-small cell lung cancer; TKI: tyrosine kinase inhibitor.

Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, Langer CJ, DeVore RF III, Gaudreault J, Damico LA, Holmgren E, Kabbinavar F. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 2004;22(11):2184–2191.

 PubMed Web of Science ®Google Scholar

Patel JD, Hensing TA, Rademaker A, Hart EM, Blum MG, Milton DT, Bonomi PD. Phase II study of pemetrexed and carboplatin plus bevacizumab with maintenance pemetrexed and bevacizumab as first-line therapy for nonsquamous non-small cell lung cancer. J Clin Oncol 2009;27(20):3284–3289.

 PubMed Web of Science ®Google Scholar

Skaff ZG, Hageboutros A, Krieger K, Coakley S, Somer R, Stevenson J. A phase II trial of first-line bevacizumab in combination with pemetrexed and carboplatin in advanced nonsquamous non-small cell lung cancer (NSCLC). J Clin Oncol 2009;27(15S). Abstract e19091.

 Google Scholar

Dalsania CJ, Hageboutros A, Harris E, Krieger K, Vora C, Stevenson J. Phase II trial of bevacizumab plus pemetrexed and carboplatin in previously untreated advanced nonsquamous non-small cell lung cancer. J Clin Oncol 2007;25(18S). Abstract 18163.

 Google Scholar

Waples JM, Auerbach M, Steis R, Boccia RV, Wiggans RG. A phase II study of oxaliplatin and pemetrexed plus bevacizumab in advanced non-squamous non-small cell lung cancer (An International Oncology Network study, #I-04–015). J Clin Oncol 2008;26(15S). Abstract 19018.

 Google Scholar

Wozniak AJ, Kalemkerian GP, Gadgeel SM, Schneider BJ, Valdivieso M, Venkatramanamoorthy R, Hackstock DM, Chen W, Heilbrun LK, Ruckdeschel JD. A phase II trial of pemetrexed (P), gemcitabine (G), and bevacizumab (BV) in untreated patients (pts) with advanced non-small cell lung cancer (NSCLC). J Clin Oncol 2009;27(15S). Abstract e19099.

 Google Scholar

Lilenbaum R, Raez L, Tseng J, Seigel L, Davila E. Efficacy and safety of oxaliplatin and gemcitabine with bevacizumab in advanced non-small cell lung cancer. J Thorac Oncol 2008;3(5):511–515.

 PubMed Web of Science ®Google Scholar

Leon L, Vazquez S, Gracia JM, Lazaro M, Firvida JL, Casal J, Amenedo M, Santome L, Gallego R, Anido U. Bevacizumab (B), cisplatin, and vinorelbine in chemotherapy-naive patients (p) with nonsquamous non-small cell lung cancer (NSCLC): a Galician Lung Cancer Group phase II study. J Clin Oncol 2009;27(15S). Abstract e19089.

 Google Scholar

Herbst RS, O'Neill VJ, Fehrenbacher L, Belani CP, Bonomi PD, Hart L, Melnyk O, Ramies D, Lin M, Sandler A. Phase II study of efficacy and safety of bevacizumab in combination with chemotherapy or erlotinib compared with chemotherapy alone for treatment of recurrent or refractory non-small cell lung cancer. J Clin Oncol 2007;25(30):4743–4750.

 PubMed Web of Science ®Google Scholar

Ferrer N, Cobo M, Paredes A, Mendez M, Munoz-Langa J, Rueda A, Alverez de Mon M, Sanchez-Hernandez A, Gallego R, Torrego J. Phase II study of bevacizumab in combination with cisplatin and docetaxel as first-line treatment of patients (p) with metastatic nonsquamous non-small cell lung cancer (NSCLC). J Clin Oncol 2009;27(15S). Abstract e19023.

 Google Scholar

Reynolds C, Barrera D, Jotte R, Spira AI, Weissman C, Boehm KA, Pritchard S, Asmar L. Phase II trial of nanoparticle albumin-bound paclitaxel, carboplatin, and bevacizumab in first-line patients with advanced nonsquamous non-small cell lung cancer. J Thorac Oncol 2009;4(12):1537–1543.

 PubMed Web of Science ®Google Scholar

Clement-Duchene C, Krupitskaya Y, Ganjoo K, Lavori P, McMillan A, Kumar A, Zhao G, Padda S, Zhou L, Pedro-Salcedo MS, Colevas AD, Wakelee HA. A phase II first-line study of gemcitabine, carboplatin, and bevacizumab in advanced stage nonsquamous non-small cell lung cancer. J Thorac Oncol 2010;5(11):1821–1825.

 PubMed Web of Science ®Google Scholar

Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006;355(24):2542–2550.

 PubMed Web of Science ®Google Scholar

Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, Leighl N, Mezger J, Archer V, Moore N, Manegold C. 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.

 PubMed Web of Science ®Google Scholar

Crino L, Dansin E, Garrido P, Griesinger F, Laskin J, Pavlakis N, Stroiakovski D, Thatcher N, Tsai CM, Wu YL, Zhou C. Safety and efficacy of first-line bevacizumab-based therapy in advanced non-squamous non-small cell lung cancer (SAiL, MO19390): a phase 4 study. Lancet Oncol 2010;11(8):733–740.

 PubMed Web of Science ®Google Scholar

Fischbach NA, Spigel D, Brahmer J, Garst J, Robles R, Chung C, Wang L, Sing A, Lynch T, for the ARIES Investigators. Preliminary safety and effectiveness of bevacizumab (BV)-based treatment in subpopulations of patients (pts) with non-small cell lung cancer (NSCLC) from the ARIES study: a bevacizumab (BV) treatment observational cohort study (OCS). J Clin Oncol 2009;27(15S). Abstract 8040.

 Google Scholar

Adjei AA, Mandrekar SJ, Dy GK, Molina JR, Adjei AA, Gandara DR, Ziegler KL, Stella PJ, Rowland KM Jr, Schild SE, Zinner RG. Phase II trial of pemetrexed plus bevacizumab for second-line therapy of patients with advanced non-small cell lung cancer: NCCTG and SWOG study N0426. J Clin Oncol 2010;28(4):614–619.

 PubMed Web of Science ®Google Scholar

Heist RS, Fidias P, Huberman M, Ardman B, Sequist LV, Temel JS, Lynch TJ. A phase II study of oxaliplatin, pemetrexed, and bevacizumab in previously treated advanced non-small cell lung cancer. J Thorac Oncol 2008;3(10):1153–1158.

 PubMed Web of Science ®Google Scholar

Flaherty KT, Schiller J, Schuchter LM, Liu G, Tuveson DA, Redlinger M, Lathia C, Xia C, Petrenciuc O, Hingorani SR, Jacobetz MA, Van Belle PA, Elder D, Brose MS, Weber BL, Albertini MR, O'Dwyer PJ. A phase I trial of the oral, multikinase inhibitor sorafenib in combination with carboplatin and paclitaxel. Clin Cancer Res 2008;14(15):4836–4842.

 PubMed Web of Science ®Google Scholar

Scagliotti G, Novello S, von PJ, Reck M, Pereira JR, Thomas M, brao Miziara JE, Balint B, de MF, Keller A, Aren O, Csollak M, Albert I, Barrios CH, Grossi F, Krzakowski M, Cupit L, Cihon F, DiMatteo S, Hanna N. Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small cell lung cancer. J Clin Oncol 2010;28(11):1835–1842.

 PubMed Web of Science ®Google Scholar

Gadgeel SM, Wozniak A, Edelman MJ, Valdivieso M, Heilbrun L, Venkatramanamoorthy R, Shields A, LoRusso P, Hackstock D, Ruckdeschel J. Cediranib, a VEGF receptor 1, 2, and 3 inhibitor, and pemetrexed in patients (pts) with recurrent non-small cell lung cancer (NSCLC). J Clin Oncol 2009;27(15S). Abstract e19007.

 Google Scholar

De Boer R, Humblet Y, Wolf J, Nogova L, Ruffert K, Milenkova T, Smith R, Godwood A, Vansteenkiste J. An open-label study of vandetanib with pemetrexed in patients with previously treated non-small cell lung cancer. Ann Oncol 2009;20(3):486–491.

 PubMed Web of Science ®Google Scholar

Heymach JV, Paz-Ares L, De BF, Sebastian M, Stewart DJ, Eberhardt WE, Ranade AA, Cohen G, Trigo JM, Sandler AB, Bonomi PD, Herbst RS, Krebs AD, Vasselli J, Johnson BE. Randomized phase II study of vandetanib alone or with paclitaxel and carboplatin as first-line treatment for advanced non-small-cell lung cancer. J Clin Oncol 2008;26(33):5407–5415.

 PubMed Web of Science ®Google Scholar

Heymach JV, Johnson BE, Prager D, Csada E, Roubec J, Pesek M, Spasova I, Belani CP, Bodrogi I, Gadgeel S, Kennedy SJ, Hou J, Herbst RS. Randomized, placebo-controlled phase II study of vandetanib plus docetaxel in previously treated non-small cell lung cancer. J Clin Oncol 2007;25(27):4270–4277.

 PubMed Web of Science ®Google Scholar

Herbst RS, Sun Y, Eberhardt WE, Germonpre P, Saijo N, Zhou C, Wang J, Li L, Kabbinavar F, Ichinose Y, Qin S, Zhang L, Biesma B, Heymach JV, Langmuir P, Kennedy SJ, Tada H, Johnson BE. 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):619–626.

 PubMed Web of Science ®Google Scholar

De Boer R, Arrieta O, Gottfried M, Blackhall FH, Raats J, Yang CH, Langmuir P, Milenkova T, Read J, Vansteenkiste J, Western Hospital, Melbourne, Australia, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico, Meir Medical Center, Kfar Saba, Israel, Christie Hospital NHS Trust, Manchester, UK, Panorama Medical Center, Capetown, South Africa, National Taiwan University Hospital, Taipei, Taiwan, AstraZeneca, Wilmington, DE, AstraZeneca, Macclesfield, UK, University Hospital Leuven, Leuven, Belgium. Vandetanib plus pemetrexed versus pemetrexed as second-line therapy in patients with advanced non-small cell lung cancer (NSCLC): a randomized, double-blind phase III trial (ZEAL). J Clin Oncol 2009;27(suppl):409s. Abstract 8010.

 Google Scholar