Plasma cytokine and angiogenic factors associated with prognosis and therapeutic response to sunitinib vs everolimus in advanced non-clear cell renal cell carcinoma.
No biomarkers are available to predict relative clinical benefit from targeted therapies in patients with non-clear cell renal cell carcinoma (nccRCC). To identify candidate predictive markers, we investigated a set of cytokines and angiogenic factors (CAFs) in previously untreated patients with nccRCC participating in the phase II ESPN trial comparing first-line sunitinib to everolimus. Pre-treatment concentrations of 30 CAFs were measured in plasma from 37 patients treated with everolimus (n=16) or sunitinib (n=21), and associated with progression-free (PFS) and overall survival (OS) after adjusting for potential confounders. High (>median) concentrations of soluble glycoprotein 130 (sgp130) were predictive of a longer PFS with sunitinib compared with everolimus (HR = 0.30; 95% CI: 0.11-0.85; P = 0.024). Significantly shorter PFS was noted, independently of treatment arm, in patients with high (>median) levels of IL-8 (HR = 3.13; 95% CI: 1.41-6.92), IL-13 (HR = 3.36; 95% CI: 1.49-7.58), and soluble tumor necrosis factor receptor II (HR = 2.21; 95% CI: 1.04-4.72). High IL-8 levels were also associated with significantly shorter OS (HR = 3.55; 95% CI: 1.55-8.14). Thus, using CAF profiling we identified candidate prognostic and predictive circulating biomarkers that can be used to inform therapeutic decisions in nccRCC.
Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Pavlos
P
Msaouel
Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Amado J
AJ
Zurita
Dan L. Duncan Cancer Center & Department of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, TX, USA.
Shixia
S
Huang
Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Eric
E
Jonasch
Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Nizar M
NM
Tannir
D043925:Angiogenesis Inducing Agents / Q000097:blood*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015415:Biomarkers; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016000:Cluster Analysis; D016207:Cytokines / Q000097:blood*; D018450:Disease Progression; D000068338:Everolimus / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D011379:Prognosis; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D016896:Treatment Outcome
D043925:Angiogenesis Inducing Agents; D000970:Antineoplastic Agents; D015415:Biomarkers; D016207:Cytokines; D007211:Indoles; D011758:Pyrroles; D000068338:Everolimus; D000077210:Sunitinib
biomarkers; cytokines and angiogenic factors; everolimus; non-clear cell renal cell carcinoma; sunitinib