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Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Multi-Center Randomized Phase II Study Comparing Cediranib plus Gefitinib with Cediranib plus Placebo in Subjects
Nicholas Brown1, Catherine McBain2, Stephen Nash3
1University College London Hospitals, London, United Kingdom.
Background:
Cediranib, an oral pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, failed to show benefit over lomustine in relapsed glioblastoma. One resistance mechanism for cediranib is up-regulation of epidermal growth factor receptor (EGFR). This study aimed to determine if dual therapy with cediranib and the oral EGFR inhibitor gefitinib improved outcome in recurrent glioblastoma.
Methods And Findings:
This was a multi-center randomized, two-armed, double-blinded phase II study comparing cediranib plus gefitinib versus cediranib plus placebo in subjects with first relapse/first progression of glioblastoma following surgery and chemoradiotherapy. The primary outcome measure was progression free survival (PFS). Secondary outcome measures included overall survival (OS) and radiologic response rate. Recruitment was terminated early following suspension of the cediranib program. 38 subjects (112 planned) were enrolled with 19 subjects in each treatment arm. Median PFS with cediranib plus gefitinib was 3.6 months compared to 2.8 months for cediranib plus placebo (HR; 0.72, 90% CI; 0.41 to 1.26). Median OS was 7.2 months with cediranib plus gefitinib and 5.5 months with cediranib plus placebo (HR; 0.68, 90% CI; 0.39 to 1.19). Eight subjects (42%) had a partial response in the cediranib plus gefitinib arm versus five patients (26%) in the cediranib plus placebo arm.
Conclusions:
Cediranib and gefitinib in combination is tolerated in patients with glioblastoma. Incomplete recruitment led to the study being underpowered. However, a trend towards improved survival and response rates with the addition of gefitinib to cediranib was observed. Further studies of the combination incorporating EGFR and VEGF inhibition are warranted.
Trial Registration:
ClinicalTrials.gov NCT01310855.
Insights
Combining cediranib and gefitinib showed a trend toward improved survival and response rates in recurrent glioblastoma patients. Despite early termination, this dual therapy is tolerated and warrants further investigation for glioblastoma treatment.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Cediranib, a VEGF receptor inhibitor, showed limited efficacy in relapsed glioblastoma.
- EGFR upregulation is a resistance mechanism to cediranib.
- This study investigated dual therapy with cediranib and gefitinib (EGFR inhibitor) for recurrent glioblastoma.
Purpose of the Study:
- To evaluate the efficacy and safety of combining cediranib with gefitinib versus cediranib with placebo in recurrent glioblastoma.
- To assess progression-free survival (PFS), overall survival (OS), and radiologic response rates.
Main Methods:
- A multi-center, randomized, double-blinded, phase II study.
- 38 patients with first relapse/progression of glioblastoma were enrolled.
- Comparison of cediranib plus gefitinib versus cediranib plus placebo.
Main Results:
- Median PFS was 3.6 months for cediranib plus gefitinib vs. 2.8 months for cediranib plus placebo.
- Median OS was 7.2 months for cediranib plus gefitinib vs. 5.5 months for cediranib plus placebo.
- Partial response rates were 42% (cediranib + gefitinib) vs. 26% (cediranib + placebo).
Conclusions:
- The combination of cediranib and gefitinib is well-tolerated in glioblastoma patients.
- The study was underpowered due to early termination but indicated a trend towards improved survival and response rates.
- Further research on combined EGFR and VEGF inhibition is recommended.
