Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/28705
Title: VEGF-A, VEGFR1 and VEGFR2 single nucleotide polymorphisms and outcomes from the AGITG MAX trial of capecitabine, bevacizumab and mitomycin C in metastatic colorectal cancer.
Austin Authors: Chionh, Fiona;Gebski, Val;Al-Obaidi, Sheren J;Mooi, Jennifer K ;Bruhn, Maressa A;Lee, Chee K;Chüeh, Anderly C;Williams, David S ;Weickhardt, Andrew J ;Wilson, Kate;Scott, Andrew M ;Simes, John;Hardingham, Jennifer E;Price, Timothy J;Mariadason, John M ;Tebbutt, Niall C 
Affiliation: Pathology
Medicine (University of Melbourne)
Medical Oncology
Molecular Imaging and Therapy
Olivia Newton-John Cancer Research Institute
Haematology-Oncology Department, Basil Hetzel Institute, The Queen Elizabeth Hospital, Woodville, SA, 5001, Australia
Department of Clinical Pathology, The University of Melbourne, Parkville, VIC, 3010, Australia
Cancer Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3168, Australia
School of Medicine, University of Adelaide, Adelaide, SA, 5005, Australia
Department of Surgery, The University of Melbourne, Parkville, VIC, 3010, Australia
School of Cancer Medicine, La Trobe University, Bundoora, VIC, 3086, Australia
NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, 2006, Australia
Issue Date: 24-Jan-2022
metadata.dc.date: 2022
Publication information: Scientific Reports 2022; 12(1): 1238
Abstract: The 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.
URI: https://ahro.austin.org.au/austinjspui/handle/1/28705
DOI: 10.1038/s41598-021-03952-y
ORCID: 0000-0001-9123-7684
0000-0003-2613-5168
0000-0002-4390-7564
0000-0002-4188-6149
0000-0003-1140-5516
0000-0003-4616-9605
0000-0002-6656-295X
0000-0003-2613-5168
PubMed URL: 35075138
PubMed URL: https://pubmed.ncbi.nlm.nih.gov/35075138/
Type: Journal Article
Appears in Collections:Journal articles

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