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Vandetanib plus pemetrexed for the second-line treatment of advanced non-small-cell lung cancer: a randomized,
Richard H de Boer1, Óscar Arrieta, Chih-Hsin Yang
1Western Hospital, Melbourne, Australia.
Purpose:
Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. This randomized, placebo-controlled phase III study assessed the efficacy of vandetanib plus pemetrexed as second-line therapy in advanced non-small-cell lung cancer.
Patients And Methods:
Patients (N = 534) were randomly assigned to receive vandetanib 100 mg/d plus pemetrexed 500 mg/m(2) every 21 days (n = 256) or placebo plus pemetrexed (n = 278). Progression-free survival (PFS) was the primary end point; overall survival, objective response rate, disease control rate, time to deterioration of symptoms, and safety were secondary assessments.
Results:
There was no significant difference in PFS between treatment arms (hazard ratio [HR], 0.86; 97.58% CI, 0.69 to 1.06; P = .108). Overall survival was also not significantly different (HR, 0.86; 97.54% CI, 0.65 to 1.13; P = .219). Statistically significant improvements in objective response rate (19% v 8%; P < .001) and time to deterioration of symptoms (HR, 0.71; P = .0052; median, 18.1 weeks for vandetanib and 12.1 weeks for placebo) were observed in patients receiving vandetanib. Adding vandetanib to pemetrexed increased the incidence of some adverse events, including rash, diarrhea, and hypertension, while showing a reduced incidence of nausea, vomiting, anemia, fatigue, and asthenia with no reduction in the dose intensity of pemetrexed.
Conclusion:
This study did not meet the primary end point of statistically significant PFS prolongation with vandetanib plus pemetrexed versus placebo plus pemetrexed. The vandetanib combination showed a significantly higher objective response rate and a significant delay in the time to worsening of lung cancer symptoms versus the placebo arm as well as an acceptable safety profile in this patient population.
Insights
Vandetanib combined with pemetrexed did not significantly extend progression-free survival in advanced non-small-cell lung cancer. However, this combination improved response rates and delayed symptom worsening, with an acceptable safety profile.
Area of Science:
- Oncology
- Pharmacology
Background:
- Vandetanib targets vascular endothelial growth factor receptor and epidermal growth factor receptor signaling pathways.
- Second-line therapy is crucial for advanced non-small-cell lung cancer (NSCLC).
Purpose of the Study:
- To evaluate the efficacy of vandetanib plus pemetrexed versus placebo plus pemetrexed as second-line treatment for advanced NSCLC.
- To assess progression-free survival (PFS) as the primary endpoint.
Main Methods:
- A randomized, placebo-controlled phase III trial involving 534 patients with advanced NSCLC.
- Patients received either vandetanib 100 mg/day plus pemetrexed 500 mg/m(2) or placebo plus pemetrexed every 21 days.
- Secondary endpoints included overall survival, objective response rate, and time to symptom deterioration.
Main Results:
- No statistically significant difference in PFS was observed between the vandetanib and placebo groups (HR, 0.86; P = .108).
- The vandetanib combination demonstrated a significantly higher objective response rate (19% vs 8%; P < .001) and delayed time to symptom deterioration (median 18.1 vs 12.1 weeks; HR, 0.71; P = .0052).
- Increased incidence of rash, diarrhea, and hypertension was noted with vandetanib, while nausea, vomiting, anemia, fatigue, and asthenia were reduced.
Conclusions:
- The study did not meet its primary endpoint of statistically significant PFS prolongation.
- Vandetanib plus pemetrexed significantly improved objective response rates and delayed symptom worsening in advanced NSCLC patients.
- The combination therapy exhibited an acceptable safety profile in this patient population.
