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dc.contributor.authorChionh, Fiona-
dc.contributor.authorGebski, Val-
dc.contributor.authorAl-Obaidi, Sheren J-
dc.contributor.authorMooi, Jennifer K-
dc.contributor.authorBruhn, Maressa A-
dc.contributor.authorLee, Chee K-
dc.contributor.authorChüeh, Anderly C-
dc.contributor.authorWilliams, David S-
dc.contributor.authorWeickhardt, Andrew J-
dc.contributor.authorWilson, Kate-
dc.contributor.authorScott, Andrew M-
dc.contributor.authorSimes, John-
dc.contributor.authorHardingham, Jennifer E-
dc.contributor.authorPrice, Timothy J-
dc.contributor.authorMariadason, John M-
dc.contributor.authorTebbutt, Niall C-
dc.identifier.citationScientific Reports 2022; 12(1): 1238en
dc.description.abstractThe phase III MAX clinical trial randomised patients with metastatic colorectal cancer (mCRC) to receive first-line capecitabine chemotherapy alone or in combination with the anti-VEGF-A antibody bevacizumab (± mitomycin C). We utilised this cohort to examine whether single nucleotide polymorphisms (SNPs) in VEGF-A, VEGFR1, and VEGFR2 are predictive of efficacy outcomes with bevacizumab or the development of hypertension. Genomic DNA extracted from archival FFPE tissue for 325 patients (69% of the MAX trial population) was used to genotype 16 candidate SNPs in VEGF-A, VEGFR1, and VEGFR2, which were analysed for associations with efficacy outcomes and hypertension. The VEGF-A rs25648 'CC' genotype was prognostic for improved PFS (HR 0.65, 95% CI 0.49 to 0.85; P = 0.002) and OS (HR 0.70, 95% CI 0.52 to 0.94; P = 0.019). The VEGF-A rs699947 'AA' genotype was prognostic for shorter PFS (HR 1.32, 95% CI 1.002 to 1.74; P = 0.048). None of the analysed SNPs were predictive of bevacizumab efficacy outcomes. VEGFR2 rs11133360 'TT' was associated with a lower risk of grade ≥ 3 hypertension (P = 0.028). SNPs in VEGF-A, VEGFR1 and VEGFR2 did not predict bevacizumab benefit. However, VEGF-A rs25648 and rs699947 were identified as novel prognostic biomarkers and VEGFR2 rs11133360 was associated with less grade ≥ 3 hypertension.en
dc.titleVEGF-A, VEGFR1 and VEGFR2 single nucleotide polymorphisms and outcomes from the AGITG MAX trial of capecitabine, bevacizumab and mitomycin C in metastatic colorectal cancer.en
dc.typeJournal Articleen
dc.identifier.journaltitleScientific Reportsen
dc.identifier.affiliationMedicine (University of Melbourne)en
dc.identifier.affiliationMedical Oncologyen
dc.identifier.affiliationMolecular Imaging and Therapyen
dc.identifier.affiliationOlivia Newton-John Cancer Research Instituteen
dc.identifier.affiliationHaematology-Oncology Department, Basil Hetzel Institute, The Queen Elizabeth Hospital, Woodville, SA, 5001, Australiaen
dc.identifier.affiliationDepartment of Clinical Pathology, The University of Melbourne, Parkville, VIC, 3010, Australiaen
dc.identifier.affiliationCancer Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3168, Australiaen
dc.identifier.affiliationSchool of Medicine, University of Adelaide, Adelaide, SA, 5005, Australiaen
dc.identifier.affiliationDepartment of Surgery, The University of Melbourne, Parkville, VIC, 3010, Australiaen
dc.identifier.affiliationSchool of Cancer Medicine, La Trobe University, Bundoora, VIC, 3086, Australiaen
dc.identifier.affiliationNHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, 2006, Australiaen
dc.identifier.pubmedid35075138-, John M
item.fulltextNo Fulltext-
item.openairetypeJournal Article-
item.languageiso639-1en- Newton-John Cancer Research Institute- Newton-John Cancer Research Institute- Newton-John Cancer Research Institute- Imaging and Therapy- Newton-John Cancer Research Institute- Newton-John Cancer Research Institute- Oncology- Newton-John Cancer Wellness and Research Centre-
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