On-target Toxicities Predictive of Survival in Metastatic Renal Cell Carcinoma (mRCC) Treated With Sunitinib: A Multicenter Retrospective Study

Clin Genitourin Cancer. 2020 Apr;18(2):e145-e156. doi: 10.1016/j.clgc.2019.10.003. Epub 2019 Dec 5.

Abstract

Background: Preliminary studies suggested that selected drug-related toxicities of sunitinib may correlate with a better prognosis.

Patients and methods: From January 2006 through December 2015, we retrospectively analyzed data of 145 patients with metastatic renal cell carcinoma treated with sunitinib as a first-line therapy in 7 different Italian oncology departments. Hypertension, hypothyroidism, thrombocytopenia, neutropenia, and anemia were evaluated. Overall survival (OS) and progression-free survival (PFS) were calculated. OS and PFS were compared in patients who developed and who did not develop a drug-related toxicity. A multivariate analysis using the Cox regression model was performed.

Results: We evaluated 145 patients (92 males; median age, 70 years); 105 (62.4%) patients experienced at least 1 toxicity: 66 (45.5%) patients developed hypothyroidism, 41 (28.3%) thrombocytopenia, 39 (26.9%) hypertension that required medical therapy, 22 (15.2%) anemia, and 11 (7.6%) neutropenia. The median PFS of patients who developed hypertension was 12 months (95% confidence interval [CI], 9-21 months) versus 9 months (95% CI, 7-12 months) in patients who did not develop toxicity; the median OS was 36 months (95% CI, 22 months to not reached) versus 26 months (95% CI, 18-34 months). For neutropenia, the median PFS was 17.5 months (95% CI, 9-65 months) versus 10 months (95% CI, 8-12 months); the median OS was 23 months (95% CI, 13 months to not reached) versus 28 months (95% CI, 22-35 months). At univariate and multivariate analysis, we observed a protective effect of hypertension and neutropenia on tumor progression (hazard ratio, 0.47; 95% CI, 0.28-0.78 and hazard ratio, 0.26; 95% CI, 0.09-0.76, respectively).

Conclusions: Many patients developed toxicities during treatment with sunitinib; hypertension and neutropenia were related to longer PFS in our cohort.

Keywords: Hypertension; Neutropenia; On target toxicities; Sunitinib; mRCC.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anemia / chemically induced
  • Anemia / epidemiology
  • Carcinoma, Renal Cell / blood
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / secondary
  • Female
  • Follow-Up Studies
  • Humans
  • Hypertension / chemically induced
  • Hypertension / epidemiology*
  • Hypothyroidism / chemically induced
  • Hypothyroidism / epidemiology
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / blood
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Neutropenia / chemically induced
  • Neutropenia / epidemiology*
  • Prognosis
  • Progression-Free Survival
  • Protective Factors
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / adverse effects
  • Retrospective Studies
  • Sunitinib / administration & dosage*
  • Sunitinib / adverse effects
  • Thrombocytopenia / chemically induced
  • Thrombocytopenia / epidemiology
  • Time Factors

Substances

  • Protein Kinase Inhibitors
  • Sunitinib