Pretreatment serum VEGF is associated with clinical response and overall survival in advanced melanoma patients treated with ipilimumab.
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.
Authors' Affiliations Melanoma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
Jianda
J
Yuan
Jun
J
Zhou
Zhiwan
Z
Dong
Sapna
S
Tandon
Deborah
D
Kuk
Katherine S
KS
Panageas
Philip
P
Wong
Xinqi
X
Wu
Jarushka
J
Naidoo
David B
DB
Page
Jedd D
JD
Wolchok
F Stephen
FS
Hodi
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy*; D008875:Middle Aged; D011379:Prognosis; D012878:Skin Neoplasms / Q000097:blood / Q000188:drug therapy*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D055815:Young Adult
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000074324:Ipilimumab; D042461:Vascular Endothelial Growth Factor A