Genetic variability of VEGF pathway genes in six randomized phase III trials assessing the addition of bevacizumab to standard therapy

Angiogenesis

Volumn 17, Issue 4, 2014, Pages 909-920

  De Haas, Sanne ^a   Delmar, Paul ^a   Bansal, Aruna T ^b   Moisse, Matthieu ^c,d   Miles, David W ^e   Leighl, Natasha ^f   Escudier, Bernard ^g   Van Cutsem, Eric ^h   Carmeliet, Peter ^c   Scherer, Stefan J ⁱ   Pallaud, Celine ^a   Lambrechts, Diether ^c,d  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

^b Acclarogen Ltd   (United Kingdom)

^c DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^d UNIVERSITY OF LEUVEN   (Belgium)

^e MOUNT VERNON CANCER CENTRE   (United Kingdom)

^f PRINCESS MARGARET HOSPITAL   (Canada)

^g INSTITUT GUSTAVE ROUSSY   (France)

^h UNIVERSITY HOSPITALS LEUVEN   (Belgium)

ⁱ GENENTECH INC   (United States)

Author keywords

Anti angiogenesis; Bevacizumab; Genetic variant; Predictive and prognostic biomarker; Treatment outcome

Indexed keywords

BEVACIZUMAB; PLACEBO; VASCULOTROPIN; ANGIOGENESIS INHIBITOR; BASIC HELIX LOOP HELIX TRANSCRIPTION FACTOR; ENDOTHELIAL PAS DOMAIN-CONTAINING PROTEIN 1; MONOCLONAL ANTIBODY; VASCULOTROPIN A; VASCULOTROPIN C; VEGFA PROTEIN, HUMAN; VEGFC PROTEIN, HUMAN; VHL PROTEIN, HUMAN; VON HIPPEL LINDAU PROTEIN;

ADULT; ADVANCED CANCER; ARTICLE; BAYES THEOREM; BREAST CANCER; COLORECTAL CANCER; CONTROLLED STUDY; DRUG EFFICACY; DRUG SAFETY; EPAS1 GENE; FEMALE; GENE; GENE EXPRESSION; GENE INTERACTION; GENE LOCUS; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC VARIABILITY; GENOTYPE; HUMAN; HUMAN CELL; IL8RA GENE; KIDNEY CANCER; LYMPHOBLASTOID CELL LINE; MAJOR CLINICAL STUDY; MALE; MALIGNANT NEOPLASTIC DISEASE; META ANALYSIS; NON SMALL CELL LUNG CANCER; PANCREAS CANCER; PHASE 3 CLINICAL TRIAL; PROGRESSION FREE SURVIVAL; RANDOMIZED CONTROLLED TRIAL; SIGNAL TRANSDUCTION; STOMACH CANCER; TREATMENT OUTCOME; VEGF A GENE; VEGF C GENE; VEGF GENE; VHL GENE; COLORECTAL NEOPLASMS; DISEASE FREE SURVIVAL; GENETICS; KAPLAN MEIER METHOD; MORTALITY; NEOPLASM; PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC);

ANGIOGENESIS INHIBITORS; ANTIBODIES, MONOCLONAL, HUMANIZED; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; BAYES THEOREM; CLINICAL TRIALS, PHASE III AS TOPIC; COLORECTAL NEOPLASMS; DISEASE-FREE SURVIVAL; GENETIC VARIATION; GENOTYPE; HUMANS; KAPLAN-MEIER ESTIMATE; NEOPLASMS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; TREATMENT OUTCOME; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VASCULAR ENDOTHELIAL GROWTH FACTOR C; VON HIPPEL-LINDAU TUMOR SUPPRESSOR PROTEIN;

EID: 84907591274     PISSN: 09696970     EISSN: 15737209     Source Type: Journal    
DOI: 10.1007/s10456-014-9438-1     Document Type: Article

References (55)

1. Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350(23):2335-2342. doi: 10.1056/NEJMoa032691
2. Sandler A, Gray R, Perry MC et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355(24):2542-2550. doi: 10.1056/NEJMoa061884
3. Miller K, Wang ML, Gralow J et al (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. New Engl J Med 357(26):2666-2676. doi: 10.1056/Nejmoa072113
4. Miles DW, Chan A, Dirix LY et al (2010) Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol 28(20):3239-3247. doi: 10.1200/JCO.2008.21.6457
5. Robert NJ, Dieras V, Glaspy J et al (2011) RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol 29(10):1252-1260. doi: 10.1200/Jco.2010.28.0982
6. Escudier B, Pluzanska A, Koralewski P et al (2007) Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 370(9605):2103-2111. doi: 10.1016/S0140-6736(07)61904-7
7. Burger RA, Brady MF, Bookman MA et al (2011) Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 365(26):2473-2483. doi: 10.1056/NEJMoa1104390
8. Perren TJ, Swart AM, Pfisterer J et al (2011) A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 365(26):2484-2496. doi: 10.1056/NEJMoa1103799
9. Aghajanian C, Blank SV, Goff BA et al (2012) OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol 30(17):2039-2045. doi: 10.1200/Jco.2012.42.0505
10. Henriksoon R, Bottomley A, Mason W, Saran F, Wick W, Nishikawa R (2013) Progression-free survival and health-related quality of life in AVAglio, a phase III study of bevacizumab, temozolomide, and radiotherapy in newly diagnosed glioblastoma. J Clin Oncol 31 (Suppl. abstr 2005). http://meetinglibrary.asco.org/content/114612-132
11. Maru D, Venook AP, Ellis LM (2013) Predictive biomarkers for bevacizumab: are we there yet? Clin Cancer Res 19(11):2824-2827. doi: 10.1158/1078-0432.Ccr-12-3409
12. Sennino B, McDonald DM (2012) Controlling escape from angiogenesis inhibitors. Nat Rev Cancer 12(10):699-709. doi: 10.1038/Nrc3366
13. Bergers G, Hanahan D (2008) Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer 8(8):592-603. doi: 10.1038/Nrc2442
14. Eichten A, Adler AP, Cooper B et al (2013) Rapid decrease in tumor perfusion following VEGF blockade predicts long-term tumor growth inhibition in preclinical tumor models. Angiogenesis 16(2):429-441. doi: 10.1007/s10456-012-9328-3
15. Lambrechts D, Lenz HJ, de Haas S, Carmeliet P, Scherer SJ (2013) Markers of response for the antiangiogenic agent bevacizumab. J Clin Oncol 31(9):1219-1230. doi: 10.1200/Jco.2012.46.2762
16. Brauer MJ, Zhuang GL, Schmidt M et al (2013) Identification and analysis of in vivo VEGF downstream markers link VEGF pathway activity with efficacy of anti-VEGF therapies. Clin Cancer Res 19(13):3681-3692. doi: 10.1158/1078-0432.Ccr-12-3635
17. Hegde PS, Jubb AM, Chen DF et al (2013) Predictive impact of circulating vascular endothelial growth factor in four phase III trials evaluating bevacizumab. Clin Cancer Res 19(4):929-937. doi: 10.1158/1078-0432.Ccr-12-2535
18. Loupakis F, Cremolini C, Fioravanti A et al (2011) Pharmacodynamic and pharmacogenetic angiogenesis-related markers of first-line FOLFOXIRI plus bevacizumab schedule in metastatic colorectal cancer. Br J Cancer 104(8):1262-1269. doi: 10.1038/Bjc.2011.85
19. Zhang W, Dahlberg SE, Yang D et al (2009) Genetic variants in angiogenesis pathway associated with clinical outcome in NSCLC patients (pts) treated with bevacizumab in combination with carboplatin and paclitaxel: subset pharmacogenetic analysis of ECOG 4599 [abstr 8032]. J Clin Oncol 27(15 Suppl.):414s. http://meetinglibrary.asco.org/content/33186-65
20. Schneider BP, Wang M, Radovich M et al (2008) Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol 26(28):4672-4678. doi: 10.1200/JCO.2008.16.1612
21. Jubb AM, Harris AL (2010) Biomarkers to predict the clinical efficacy of bevacizumab in cancer. Lancet Oncol 11(12):1172-1183. doi: 10.1016/S1470-2045(10)70232-1
22. Gerger A, El-Khoueiry A, Zhang W et al (2011) Pharmacogenetic angiogenesis profiling for first-line bevacizumab plus oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Clin Cancer Res 17(17):5783-5792. doi: 10.1158/1078-0432.CCR-11-1115
23. Lambrechts D, Claes B, Delmar P et al (2012) VEGF pathway genetic variants as biomarkers of treatment outcome with bevacizumab: an analysis of data from the AViTA and AVOREN randomised trials. Lancet Oncol 13(7):724-733. doi: 10.1016/S1470-2045(12)70231-0
24. Hansen TF, Christensen RD, Andersen RF, Spindler KLG, Johnsson A, Jakobsen A (2012) The predictive value of single nucleotide polymorphisms in the VEGF system to the efficacy of first-line treatment with bevacizumab plus chemotherapy in patients with metastatic colorectal cancer results from the Nordic ACT trial. Int J Colorectal Dis 27(6):715-720. doi: 10.1007/S00384-011-1382-6
25. Schneider BP, Gray RJ, Radovich M et al (2013) Prognostic and predictive value of tumor vascular endothelial growth factor gene amplification in metastatic breast cancer treated with paclitaxel with and without bevacizumab; results from ECOG 2100 trial. Clin Cancer Res 19(5):1281-1289. doi: 10.1158/1078-0432.Ccr-12-3029
26. Loupakis F, Cremolini C, Dongyun Y et al (2013) Prospective validation of candidate SNPs of VEGF/VEGFR pathway in metastatic colorectal cancer patients treated with first-line FOLFIRI plus bevacizumab. Plos One 8(7):e66774. doi: 10.1371/journal.pone.0066774
27. Van Cutsem E, Vervenne WL, Bennouna J et al (2009) Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. J Clin Oncol 27(13):2231-2237. doi: 10.1200/JCO.2008.20.0238
28. Reck M, von Pawel J, Zatloukal P et al (2009) Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAiL. J Clin Oncol 27(8):1227-1234. doi: 10.1200/Jco.2007.14.5466
29. Ohtsu A, Shah MA, Van Cutsem E et al (2011) Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol 29(30):3968-3976. doi: 10.1200/Jco.2011.36.2236
30. Barret JC (2009) Haploview: visualization and analysis of SNP genotype data. Cold Spring Harb Protoc 10:pdb.ip71. doi: 10.1101/pdb.ip71
31. Pettersson FH, Anderson CA, Clarke GM et al (2009) Marker selection for genetic case-control association studies. Nat Protoc 4(5):743-752. doi: 10.1038/Nprot.2009.38
32. Lambrechts D, Moisse M, Delmar P et al (2014) Genetic markers of bevacizumab-induced hypertension. Angiogenesis. doi: 10.1007/s10456-014-9424-7
33. Grundberg E, Small KS, Hedman AK et al (2012) Mapping cis- and trans-regulatory effects across multiple tissues in twins. Nat Genet 44(10):1084-1089. doi: 10.1038/ng.2394
34. Yang TP, Beazley C, Montgomery SB et al (2010) Genevar: a database and Java application for the analysis and visualization of SNP-gene associations in eQTL studies. Bioinformatics 26(19):2474-2476. doi: 10.1093/bioinformatics/btq452
35. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate - a practical and powerful approach to multiple testing. J R Stat Soc B 57(1):289-300
36. Goeman JJ, van de Geer SA, de Kort F, van Houwelingen HC (2004) A global test for groups of genes: testing association with clinical outcome. Bioinformatics 20:93-99
37. Goeman JJ, Oosting J, Cleton-Jansen AM, Anninga JK, van Houwelingen HC (2005) Testing association of a pathway with survival using gene expression data. Bioinformatics 21(9):1950-1957. doi: 10.1093/Bioinformatics/Bti267
38. Zou H, Hastie T (2005) Regularization and variable selection via the elastic net. J R Stat Soc B 67:301-320. doi: 10.1111/J.1467-9868.2005.00503.X
39. Friedman J, Hastie T, Tibshirani R (2008) Regularization paths for generalized linear models via coordinate descent. J Stat Soft 33:1-22
40. Simon N, Friedman J, Hastie T, Tibshirani R (2011) Regularization paths for Cox's proportional hazards model via coordinate descent. J Stat Soft 39:1-13
41. Choi I, Lee YS, Chung HK et al (2013) Interleukin-8 reduces post-surgical lymphedema formation by promoting lymphatic vessel regeneration. Angiogenesis 16(1):29-44. doi: 10.1007/s10456-012-9297-6
42. Nakata I, Yamashiro K, Nakanishi H, Tsujikawa A, Otani A, Yoshimura N (2011) VEGF gene polymorphism and response to intravitreal bevacizumab and triple therapy in age-related macular degeneration. Jpn J Ophthalmol 55(5):435-443. doi: 10.1007/S10384-011-0061-Z
43. Chen J, Michan S, Juan AM et al (2013) Neuronal sirtuin1 mediates retinal vascular regeneration in oxygen-induced ischemic retinopathy. Angiogenesis 16(4):985-992. doi: 10.1007/s10456-013-9374-5
44. Xia GB, Kageyama Y, Hayashi T, Kawakami S, Yoshida M, Kihara M (2001) Regulation of vascular endothelial growth factor transcription by endothelial PAS domain protein 1 (EPAS1) and possible involvement of EPAS1 in the angiogenesis of renal cell carcinoma. Cancer 91(8):1429-1436. doi: 10.1002/1097-0142(20010415)91:8<1429:Aid-Cncr1149>3.0.Co;2-V
45. Favier J, Plouin PF, Corvol P, Gasc JM (2002) Angiogenesis and vascular architecture in pheochromocytomas - distinctive traits in malignant tumors. Am J Pathol 161(4):1235-1246. doi: 10.1016/S0002-9440(10)64400-8
46. Favier J, Lapointe S, Maliba R, Sirois MG (2007) HIF2 alpha reduces growth rate but promotes angiogenesis in a mouse model of neuroblastoma. BMC Cancer 7. doi: 10.1186/1471-2407-7-139
47. Keith B, Johnson RS, Simon MC (2011) HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression. Nat Rev Cancer 12:9-22
48. Jubb AM, Turley H, Moeller HC et al (2009) Expression of delta-like ligand 4 (Dll4) and markers of hypoxia in colon cancer. Br J Cancer 101(10):1749-1757. doi: 10.1038/Sj.Bjc.6605368
49. Talks KL, Turley H, Gatter KC et al (2000) The expression and distribution of the hypoxia-inducible factors HIF-1 alpha and HIF-2 alpha in normal human tissues, cancers, and tumor-associated macrophages. Am J Pathol 157(2):411-421. doi: 10.1016/S0002-9440(10)64554-3
50. Shay JES, Simon MC (2012) Hypoxia-inducible factors: crosstalk between inflammation and metabolism. Semin Cell Dev Biol 23(4):389-394. doi: 10.1016/J.Semcdb.04.004
51. Simonson TS, Yang YZ, Huff CD et al (2010) Genetic evidence for high-altitude adaptation in Tibet. Science 329(5987):72-75. doi: 10.1126/Science.1189406
52. Yi X, Liang Y, Huerta-Sanchez E et al (2010) Sequencing of 50 human exomes reveals adaptation to high altitude. Science 329(5987):75-78. doi: 10.1126/Science.1190371
53. Beall CM, Cavalleri GL, Deng LB et al (2010) Natural selection on EPAS1 (HIF2 alpha) associated with low hemoglobin concentration in Tibetan highlanders. Proc Natl Acad Sci USA 107(25):11459-11464. doi: 10.1073/Pnas.1002443107
54. Lambrechts D, Storkebaum E, Morimoto M et al (2003) VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death. Nat Genet 34(4):383-394. doi: 10.1038/ng1211
55. Han SW, Kim GW, Seo JS et al (2004) VEGF gene polymorphisms and susceptibility to rheumatoid arthritis. Rheumatology (Oxf) 43(9):1173-1177. doi: 10.1093/rheumatology/keh281