Baseline vascular endothelial growth factor concentration as a potential predictive marker of benefit from vandetanib in non-small cell lung cancer.
PURPOSE: Vandetanib [vascular endothelial growth factor (VEGF) receptor/epidermal growth factor receptor/RET inhibitor] has shown improvements in progression-free survival (PFS) in advanced non-small cell lung cancer in three randomized phase II studies: vandetanib versus gefitinib (study 3), docet...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2009
|
| _version_ | 1826307390522261504 |
|---|---|
| author | Hanrahan, E Ryan, A Mann, H Kennedy, S Langmuir, P Natale, R Herbst, R Johnson, B Heymach, J |
| author_facet | Hanrahan, E Ryan, A Mann, H Kennedy, S Langmuir, P Natale, R Herbst, R Johnson, B Heymach, J |
| author_sort | Hanrahan, E |
| collection | OXFORD |
| description | PURPOSE: Vandetanib [vascular endothelial growth factor (VEGF) receptor/epidermal growth factor receptor/RET inhibitor] has shown improvements in progression-free survival (PFS) in advanced non-small cell lung cancer in three randomized phase II studies: vandetanib versus gefitinib (study 3), docetaxel +/- vandetanib (study 6), and carboplatin-paclitaxel and/or vandetanib (study 7). In study 7, vandetanib monotherapy was inferior to carboplatin-paclitaxel. We performed an exploratory retrospective analysis of the relationship between baseline circulating VEGF concentrations and PFS. EXPERIMENTAL DESIGN: Mean baseline VEGF levels were determined by ELISA from two baseline samples of plasma (163 of 168 patients, study 3; 65 of 127, study 6) or serum (144 of 181, study 7). High baseline VEGF values were above the immunoassay reference range for healthy subjects; low baseline VEGF values were within the range. RESULTS: Patients with low baseline VEGF had a lower risk of disease progression with vandetanib versus gefitinib [hazard ratio (HR), 0.55; 95% confidence interval (95% CI), 0.35-0.86; P = 0.01] or vandetanib 100 mg/d + docetaxel versus docetaxel (HR, 0.25; 95% CI, 0.09-0.68; P = 0.01). High VEGF patients had a similar risk of disease progression with vandetanib monotherapy versus gefitinib (HR, 1.03; 95% CI, 0.60-1.75; P = 0.92) or vandetanib 100 mg/d + docetaxel versus docetaxel (HR, 0.95; 95% CI, 0.25-3.61; P = 0.94). In study 7, low VEGF patients had a similar risk of disease progression with vandetanib monotherapy 300 mg/d versus carboplatin-paclitaxel (HR, 0.80; 95% CI, 0.41-1.56; P = 0.51); high VEGF patients progressed more quickly (HR, 1.60; 95% CI, 0.81-3.15; P = 0.17). CONCLUSIONS: These analyses suggest that low baseline circulating VEGF may be predictive of PFS advantage in patients with advanced non-small cell lung cancer receiving vandetanib versus gefitinib or vandetanib + docetaxel versus docetaxel. Moreover, patients with low VEGF levels may have a similar outcome with either vandetanib monotherapy or carboplatin-paclitaxel. |
| first_indexed | 2024-03-07T07:02:24Z |
| format | Journal article |
| id | oxford-uuid:ffeffc6f-ea11-4fc6-8fe4-8328b7e5cf2a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:02:24Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:ffeffc6f-ea11-4fc6-8fe4-8328b7e5cf2a2022-03-27T13:48:53ZBaseline vascular endothelial growth factor concentration as a potential predictive marker of benefit from vandetanib in non-small cell lung cancer.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ffeffc6f-ea11-4fc6-8fe4-8328b7e5cf2aEnglishSymplectic Elements at Oxford2009Hanrahan, ERyan, AMann, HKennedy, SLangmuir, PNatale, RHerbst, RJohnson, BHeymach, J PURPOSE: Vandetanib [vascular endothelial growth factor (VEGF) receptor/epidermal growth factor receptor/RET inhibitor] has shown improvements in progression-free survival (PFS) in advanced non-small cell lung cancer in three randomized phase II studies: vandetanib versus gefitinib (study 3), docetaxel +/- vandetanib (study 6), and carboplatin-paclitaxel and/or vandetanib (study 7). In study 7, vandetanib monotherapy was inferior to carboplatin-paclitaxel. We performed an exploratory retrospective analysis of the relationship between baseline circulating VEGF concentrations and PFS. EXPERIMENTAL DESIGN: Mean baseline VEGF levels were determined by ELISA from two baseline samples of plasma (163 of 168 patients, study 3; 65 of 127, study 6) or serum (144 of 181, study 7). High baseline VEGF values were above the immunoassay reference range for healthy subjects; low baseline VEGF values were within the range. RESULTS: Patients with low baseline VEGF had a lower risk of disease progression with vandetanib versus gefitinib [hazard ratio (HR), 0.55; 95% confidence interval (95% CI), 0.35-0.86; P = 0.01] or vandetanib 100 mg/d + docetaxel versus docetaxel (HR, 0.25; 95% CI, 0.09-0.68; P = 0.01). High VEGF patients had a similar risk of disease progression with vandetanib monotherapy versus gefitinib (HR, 1.03; 95% CI, 0.60-1.75; P = 0.92) or vandetanib 100 mg/d + docetaxel versus docetaxel (HR, 0.95; 95% CI, 0.25-3.61; P = 0.94). In study 7, low VEGF patients had a similar risk of disease progression with vandetanib monotherapy 300 mg/d versus carboplatin-paclitaxel (HR, 0.80; 95% CI, 0.41-1.56; P = 0.51); high VEGF patients progressed more quickly (HR, 1.60; 95% CI, 0.81-3.15; P = 0.17). CONCLUSIONS: These analyses suggest that low baseline circulating VEGF may be predictive of PFS advantage in patients with advanced non-small cell lung cancer receiving vandetanib versus gefitinib or vandetanib + docetaxel versus docetaxel. Moreover, patients with low VEGF levels may have a similar outcome with either vandetanib monotherapy or carboplatin-paclitaxel. |
| spellingShingle | Hanrahan, E Ryan, A Mann, H Kennedy, S Langmuir, P Natale, R Herbst, R Johnson, B Heymach, J Baseline vascular endothelial growth factor concentration as a potential predictive marker of benefit from vandetanib in non-small cell lung cancer. |
| title | Baseline vascular endothelial growth factor concentration as a potential predictive marker of benefit from vandetanib in non-small cell lung cancer. |
| title_full | Baseline vascular endothelial growth factor concentration as a potential predictive marker of benefit from vandetanib in non-small cell lung cancer. |
| title_fullStr | Baseline vascular endothelial growth factor concentration as a potential predictive marker of benefit from vandetanib in non-small cell lung cancer. |
| title_full_unstemmed | Baseline vascular endothelial growth factor concentration as a potential predictive marker of benefit from vandetanib in non-small cell lung cancer. |
| title_short | Baseline vascular endothelial growth factor concentration as a potential predictive marker of benefit from vandetanib in non-small cell lung cancer. |
| title_sort | baseline vascular endothelial growth factor concentration as a potential predictive marker of benefit from vandetanib in non small cell lung cancer |
| work_keys_str_mv | AT hanrahane baselinevascularendothelialgrowthfactorconcentrationasapotentialpredictivemarkerofbenefitfromvandetanibinnonsmallcelllungcancer AT ryana baselinevascularendothelialgrowthfactorconcentrationasapotentialpredictivemarkerofbenefitfromvandetanibinnonsmallcelllungcancer AT mannh baselinevascularendothelialgrowthfactorconcentrationasapotentialpredictivemarkerofbenefitfromvandetanibinnonsmallcelllungcancer AT kennedys baselinevascularendothelialgrowthfactorconcentrationasapotentialpredictivemarkerofbenefitfromvandetanibinnonsmallcelllungcancer AT langmuirp baselinevascularendothelialgrowthfactorconcentrationasapotentialpredictivemarkerofbenefitfromvandetanibinnonsmallcelllungcancer AT nataler baselinevascularendothelialgrowthfactorconcentrationasapotentialpredictivemarkerofbenefitfromvandetanibinnonsmallcelllungcancer AT herbstr baselinevascularendothelialgrowthfactorconcentrationasapotentialpredictivemarkerofbenefitfromvandetanibinnonsmallcelllungcancer AT johnsonb baselinevascularendothelialgrowthfactorconcentrationasapotentialpredictivemarkerofbenefitfromvandetanibinnonsmallcelllungcancer AT heymachj baselinevascularendothelialgrowthfactorconcentrationasapotentialpredictivemarkerofbenefitfromvandetanibinnonsmallcelllungcancer |