BACKGROUND: Treatment of patients with metastatic renal cell carcinoma (mRCC) has improved substantially since the introduction of targeted therapies, but no predictive biomarkers are available. The proto-oncogene c-Met is involved in tumor angiogenesis, development, and metastasis. The main objective was to evaluate c-Met expression in sunitinib-treated patients with mRCC, including patients with bone metastases. METHODS: c-Met expression was analyzed from 137 formalin-fixed paraffin-embedded tumor samples using a validated immunostaining protocol. RESULTS: Patients with low c-Met expression (n = 78) had longer progression-free survival (PFS) (median 14.3 vs. 6.5 months; P < .001) and overall survival (OS) (median 32.1 vs. 20.1 months; P = .049) than those with high expression. High c-Met expression was an independent predictor of unfavorable PFS in a Cox proportional hazards model adjusted for the Heng risk criteria (HR 1.60 [1.09-2.35]; P = .016). In a subgroup of patients with no bone metastases (n = 106), low c-Met expression was associated with a both longer OS (unadjusted HR 0.63 [95% CI, 0.42-0.95]; P = .034) and PFS (unadjusted HR 0.47 [95% CI, 0.31-0.71]; P < .001). CONCLUSIONS: High c-Met expression was associated with poor survival in patients with mRCC treated with sunitinib. Interestingly, the prognostic role may vary based on the location of metastases.
BACKGROUND: Treatment of patients with metastatic renal cell carcinoma (mRCC) has improved substantially since the introduction of targeted therapies, but no predictive biomarkers are available. The proto-oncogene c-Met is involved in tumor angiogenesis, development, and metastasis. The main objective was to evaluate c-Met expression in sunitinib-treated patients with mRCC, including patients with bone metastases. METHODS:c-Met expression was analyzed from 137 formalin-fixed paraffin-embedded tumor samples using a validated immunostaining protocol. RESULTS:Patients with low c-Met expression (n = 78) had longer progression-free survival (PFS) (median 14.3 vs. 6.5 months; P < .001) and overall survival (OS) (median 32.1 vs. 20.1 months; P = .049) than those with high expression. High c-Met expression was an independent predictor of unfavorable PFS in a Cox proportional hazards model adjusted for the Heng risk criteria (HR 1.60 [1.09-2.35]; P = .016). In a subgroup of patients with no bone metastases (n = 106), low c-Met expression was associated with a both longer OS (unadjusted HR 0.63 [95% CI, 0.42-0.95]; P = .034) and PFS (unadjusted HR 0.47 [95% CI, 0.31-0.71]; P < .001). CONCLUSIONS: High c-Met expression was associated with poor survival in patients with mRCC treated with sunitinib. Interestingly, the prognostic role may vary based on the location of metastases.
Authors: Aly-Khan A Lalani; Kathryn P Gray; Laurence Albiges; Marcella Callea; Jean-Christophe Pignon; Soumitro Pal; Mamta Gupta; Rupal S Bhatt; David F McDermott; Michael B Atkins; G F Vande Woude; Lauren C Harshman; Toni K Choueiri; Sabina Signoretti Journal: Oncotarget Date: 2017-10-23