Current status of vandetanib (ZD6474) in the treatment of non-small cell lung cancer

Figures & data

Table 1 Randomized NSCLC clinical trials evaluating vandetanib

Study # Pts # prior chemo	Design	RR (%)	PFS*	OS (m)
Randomized Phase II Trials
Kiura 2008^Citation38 53/1–2	All arms 1. V 100 mg 2. V 200 mg 3. V 300 mg	13 17.6 5.6 16.7	TTP 8.3 weeks 12.3 weeks 12.3 weeks	–
Natale 2009^Citation39 168/1–2	1. V 300 mg 2. Gefitinib 250 mg daily; crossover allowed	8 1	8.1 weeks 11.3 weeks HR .69, P = 0.013;	6.1 7.4 NS
Heymach 2007^Citation40 127/1	1. Docetaxel + V 100 mg 2. Docetaxel + V 300 mg 3. Docetaxel	26 18 12	18.7 weeks^ 17 weeks 12 weeks^ ^HR 0.64, P = 0.037	13.1 7.9 13.4
Heymach 2008^Citation41 181/chemonaive	1. Carboplatin/Paclitaxel + V 300 mg 2. Carboplatin/Paclitaxel 3. V 300 mg	32 25	24 weeks (1). 23 weeks (2) HR 0.76; P = 0.098 [V alone arm closed]	10.2 12.6 NS
Phase III Trials
Natale 2009^Citation49 ZEST 1240/1–2	1. V 300 mg 2. Erlotinib	12 12	11.3 weeks 8.9 weeks HR 0.98; P = 0.721	6.9 7.8 NS
De Boer 2009^Citation50 ZEAL 534/1	1. Pemetrexed + V 100 mg 2. Pemetrexed	19 8	17.6 weeks 11.9 weeks HR 0.86; P = 0.108	10.5 9.2 NS
Herbst 2009^Citation51 ZODIAC 1391/1	1. Docetaxel + V 100 mg 2. Docetaxel	17 10	4 months 3.2 months HR 0.79; P <0.001	10.6 10 NS

Note:

* PFS primary endpoint of all trials except Kiura et al study³⁸ where RR was primary endpoint.

Abbreviations: RR, response rate; PFS, progression-free survival; OS, overall survival; m, months; TTP, time to progression; V, vandetanib (given once daily in all studies); NS, not statistically significant.

Table 2 Ongoing/pending trials of vandetanib in NSCLC

Sponsor/trial	Phase	Target N	Eligibility	Treatment	Primary endpoint
AstraZeneca^Citation52 ZEPHYR NCT00404924	III	930	– Prior treatment with an EGFR TKI and up to 2 chemo regimens	1. BSC + V 300 2. BSC	OS
AstraZeneca^Citation53 NCT00753714	RII	122	– No prior chemo – ≥70 years of age	1. gemcitabine +V 100 2. gemcitabine	PFS
PrECOG, LLC.^Citation54 NCT00687297	RII	160	– No prior therapy for advanced NSCLC	1. Docetaxel/carboplatin/V 100 + maintenance V 300 2. Docetaxel/carboplatin/V 100	PFS
AstraZeneca^Citation55 NCT00777179	RII	126	– No POD after 4 cycles of gemcitabine/cisplatin for advanced NSCLC	1. Maintenance V 300 2. Placebo	PFS
MD Anderson^Citation56 NCT00745732	I/II	48	– Inoperable/unresectable NSCLC, not candidate for chemo	Escalating doses of V starting at 100 mg + thoracic irradiation	MTD
AstraZeneca^Citation57 NCT00807170	I	18	– Untreated brain metastases	V 100/200/300 + WBRT	MTD
MD Anderson^Citation58 BATTLE NCT00410189	II	72	– At least one prior chemo for advanced NSCLC	V 300 (biomarker directed)	PFS
MD Anderson^Citation59 NCT00402896	II	25	– Symptomatic recurrent pleural effusion	V 300	Time until removal of pleurex catheter
Simmons Cancer Center^Citation60 NCT00975260 *Not yet open	R I/II	72	Stage IIIA/B NSCLC	1. Definitive CRT with carboplatin/paclitaxel + V followed by maintenance V 2. Definitive CRT with carboplatin/paclitaxel	OS
Karmanos Cancer Institute ^Citation61 NCT00459121	II	15	Clinical Stage IB, II, and T3N1 NSCLC	Neoadjuvant carboplatin/paclitaxel + V	Complete resection (R0) *trial completed, awaiting results
AstraZeneca^Citation62 NCT00496275	I	17	Chemonaive advanced disease	Cisplatin/gemcitabine/V Cisplatin/vinorelbine/V	Safety *trial completed, awaiting results

Abbreviations: N, number of patients; EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor; BSC, best supportive care; V, vandetanib given once daily; R, randomized; POD, progression of disease; PFS, progression-free survival; MTD, maximum tolerated dose; WBRT, whole brain irradiation; CRT, chemoradiation; OS, overall survival.

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