Entry Detail
| General information | |
| Database: | DB01012 |
| Objective: | Vandetanib is a oncedaily oral inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor (EGFR), and RET signaling. This placebocontrolled trial assessed whether vandetanib conferred an overall survival benefit in patients with advanced non small cell lung cancer (non small cell lung cancer) after prior treatment with an EGFR tyrosine kinase inhibitor and one or two chemotherapy regimens. |
| Authors: | Lee JS, et al |
| Title: | 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, doubleblindphase III trial (ZEPHYR). |
| Journal: | J Clin Oncol. |
| Year: | 2012 |
| PMID: | 22370318 |
| Trial Design | |
| Clinical Trial Id: | NCT00404924 |
| Agent: | vandetanib |
| Target: | Epidermal growth factor receptor Vascular endothelial growth factor receptor 2 Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced non small cell lung cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a randomized, doubleblindphase III trial (ZEPHYR). |
| Key Patients Feature: | patients with advanced non small cell lung cancer after prior therapy with an epidermal growth factor receptor tyrosine kinase inhibitor |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | Vandetanib Versus placebo |
| Treatment Info: | Eligible patients were randomly assigned 2:1 to receive vandetanib 300 mg/d or placebo until disease progression or unacceptable toxicity |
| Primary End Point: | overall survival. |
| Secondary End Point: | NA |
| Patients Number: | 924 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | 2.6% v 0.7% |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 1.9 months with vandetanib and 1.8 months with placebo |
| Median OS A vs. C: | 8.5 months versus 7.8 months for vandetanib and placebo patients, respectively. |
| Adverse Event(agent arm): | The most common adverse events in the vandetanib arm were consistent with pharmacodynamic inhibition of EGFR (skin reactions, diarrhea) and/or VEGFR signaling (hypertension). It is notable that the majority of patients were able to continue receiving study treatment without dose interruption or reduction or discontinuation of study treatment. The median duration of exposure to randomized treatment was similar across both patient cohorts; however, more patients in the vandetanib cohort experienced adverse events, including grade more than and equal to 3 adverse events, serious adverse events, and adverse events leading to discontinuation of study treatment. |
| Conclusions: | The study did not demonstrate an overall survival benefit for vandetanib versus placebo. There was a higher incidence of some adverse events with vandetanib. |