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Vandetanib versus gefitinib in patients with advanced non-small-cell lung cancer: results from a two-part,
Ronald B Natale1, David Bodkin, Ramaswamy Govindan
1Cedars-Sinai Outpatient Cancer Center, Los Angeles, CA 90048, USA. Ronald.Natale@cshs.org
Purpose:
Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) signaling. In this two-part phase II study, the efficacy and safety of vandetanib was compared with that of gefitinib, an inhibitor of EGFR signaling.
Patients And Methods:
Patients (N = 168) with locally advanced or metastatic (stage IIIB/IV) non-small-cell lung cancer (NSCLC), after failure of first-line with or without second-line platinum-based chemotherapy, received once-daily vandetanib 300 mg (n = 83) or gefitinib 250 mg (n = 85) until disease progression or evidence of toxicity (part A). After a 4-week washout period, eligible patients had the option to switch to the alternative treatment (part B). Progression-free survival (PFS) was the primary efficacy assessment in part A, which was designed to have a higher than 75% power to detect a 33% prolongation of PFS at a one-sided significance level of .2.
Results:
In part A, vandetanib prolonged PFS compared with gefitinib (hazard ratio = 0.69; 95% CI, 0.50 to 0.96; one-sided P = .013). Patients receiving vandetanib experienced adverse events that were manageable and generally consistent with inhibition of EGFR and VEGFR signaling, including diarrhea, rash, and hypertension. There were no unexpected safety findings with gefitinib. Overall survival, a secondary assessment, was not significantly different between patients initially randomly assigned to either vandetanib or gefitinib.
Conclusion:
The primary efficacy objective was achieved, with vandetanib demonstrating a significant prolongation of PFS versus gefitinib. Vandetanib 300 mg/d is currently being evaluated as a monotherapy in two randomized phase III studies in advanced NSCLC.
Insights
Vandetanib significantly improved progression-free survival in patients with advanced non-small-cell lung cancer compared to gefitinib. This study highlights vandetanib
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer mortality.
- Targeted therapies inhibiting vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) signaling pathways are crucial in NSCLC treatment.
- Gefitinib, an EGFR inhibitor, is a standard treatment, but resistance and limited efficacy necessitate novel therapeutic strategies.
Purpose of the Study:
- To compare the efficacy and safety of vandetanib, a dual VEGFR and EGFR inhibitor, against gefitinib in patients with advanced NSCLC.
- To evaluate progression-free survival (PFS) as the primary endpoint in a phase II clinical trial setting.
- To assess overall survival and adverse events associated with vandetanib and gefitinib treatment.
Main Methods:
- A two-part, randomized phase II study involving 168 patients with locally advanced or metastatic NSCLC.
- Patients received either vandetanib (300 mg once daily) or gefitinib (250 mg once daily) until disease progression or toxicity.
- Progression-free survival (PFS) was the primary efficacy endpoint, with overall survival as a secondary assessment.
Main Results:
- Vandetanib demonstrated a statistically significant prolongation of PFS compared to gefitinib (hazard ratio = 0.69; P = .013).
- Adverse events with vandetanib, including diarrhea, rash, and hypertension, were manageable and consistent with its mechanism of action.
- No significant difference in overall survival was observed between the vandetanib and gefitinib treatment arms.
Conclusions:
- Vandetanib significantly improved progression-free survival in advanced NSCLC patients compared to gefitinib, achieving the primary efficacy objective.
- Vandetanib exhibits a manageable safety profile in this patient population.
- Further evaluation of vandetanib as monotherapy in advanced NSCLC is ongoing in phase III trials.
