Pretreatment serum VEGF is associated with clinical response and overall survival in advanced melanoma patients treated with ipilimumab Journal Article


Authors: Yuan, J. D.; Zhou, J.; Dong, Z.; Tandon, S.; Kuk, D.; Panageas, K. S.; Wong, P.; Wu, X. Q.; Naidoo, J.; Page, D. B.; Wolchok, J. D.; Hodi, F. S.
Article Title: Pretreatment serum VEGF is associated with clinical response and overall survival in advanced melanoma patients treated with ipilimumab
Abstract: Ipilimumab, an antibody that blocks CTL antigen 4 (CTLA-4), improves overall survival (OS) for patients with metastatic melanoma. Given its role in angiogenesis and immune evasion, serum VEGF levels were evaluated for association with clinical benefit in ipilimumab-treated patients. Sera were collected from 176 patients treated at 3 (n = 98) or 10 mg/kg (n = 68). The VEGF levels before treatment and at induction completion (week 12) were analyzed using the Meso Scale Discovery kit. The association of the levels of VEGF with clinical responses and OS were assessed using the Fisher exact and Kaplan-Meier log-rank tests. VEGF as a continuous variable was associated with OS (P = 0.002). Using 43 pg/mL as the cutoff pretreatment VEGF value defined by maximally selected log-rank statistics, pretreatment VEGF values correlated with clinical benefit at week 24 (P = 0.019; 159 patients evaluable). Pretreatment VEGF >= 43 pg/mL was associated with decreased OS (median OS 6.6 vs. 12.9 months, P = 0.006; 7.4 vs. 14.3 months, P = 0.037 for 3 mg/kg; and 6.2 vs. 10.9 months, P = 0.048 for 10 mg/kg). There was no correlation between VEGF changes and clinical outcome. Serum VEGF may be a predictive biomarker for ipilimumab treatment and is worthy of prospective investigation with various forms of immunologic checkpoint blockade. (C) 2014 AACR.
Keywords: immunotherapy; ctla-4; metastatic melanoma; lymphocyte-associated antigen-4; antibody blockade; responses; t-cell; benefit; angiogenic factors; growth-factor receptor-1; cancer
Journal Title: Cancer Immunology Research
Volume: 2
Issue: 2
ISSN: 2326-6066
Publisher: American Association for Cancer Research  
Date Published: 2014-02-01
Start Page: 127
End Page: 132
Language: English
ACCESSION: WOS:000340031200006
DOI: 10.1158/2326-6066.cir-13-0163
PROVIDER: wos
PUBMED: 24778276
PMCID: PMC3991109
Notes: Article -- Source: Wos
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MSK Authors
  1. Jedd D Wolchok
    905 Wolchok
  2. Phillip Wong
    81 Wong
  3. Katherine S Panageas
    519 Panageas
  4. Jianda Yuan
    105 Yuan
  5. Deborah Kuk
    87 Kuk
  6. Zhiwan Dong
    8 Dong
  7. Sapna Tandon
    5 Tandon
  8. David B Page
    30 Page
  9. Jarushka Naidoo
    33 Naidoo