238O - Phase II study of pazopanib as second-line treatment after sunitinib in patients with metastatic renal cell carcinoma

Date 19 December 2015
Event ESMO Asia 2015 Congress
Session Genitourinary tumours
Topics Anti-Cancer Agents & Biologic Therapy
Renal Cell Cancer
Presenter Mian Xie
Citation Annals of Oncology (2015) 26 (suppl_9): 71-79. 10.1093/annonc/mdv524
Authors C. He1, M. Xie2, J. Huang1
  • 1Nephrology, Guangdong General Hospital, Guangzhou/CN
  • 2Translational Reasearch, The 1st Affiliated Hospital of Guangzhou Medical University, 510120 - Guangzhou/CN

Abstract

Aim/Background

The multicentre, single arm, phase 2 study was aimed to assess the efficacy and safety of pazopanib as second line treatment after failure of sunitinib in patients with metastatic renal cell carcinoma (mRCC) and explore biomarkers for pazopanib response.

Methods

Patients received pazopanib 800 mg per day. The primary end point was progression free survival (PFS). Secondary end points included objective response rate (ORR), overall survival (OS) and safety. Serum protein levels of delta like ligand (DLL4), Notch1, hypoxia inducible factor factor 1A (HIF1A), HIF2A, vascular endothelial growth factor A (VEGFA) and platelet derived growth factor receptor B (PDGFRB) were measured using enzyme linked immunosorbent assay (ELISA).

Results

86 patients with clear cell mRCC were enrolled from December 2009 to March 2012 from three centres in Southern China. Of 85 evaluable patients, the median PFS was 5.6 months (95% confidence interval (CI), 4.1 to 6.7 months) by independent review. No complete response (CR) was observed in all patients. 13 patients achieved partial responses (PR) (ORR 15.3%; 95% CI, 11.2 to 23.9%). Median OS was 18.1 months (95% CI, 13.2 to 19.8 months). The most common adverse events (AEs) were mild to moderate and clinically manageable, including hypertension (37.6%), diarrhea (36.5%), increased AST (51.8%), and anaemia (60%). AEs resulted in dose reduction in 24.7% of patients. Multivariable analysis showed that higher baseline levels of DLL4 and VEGFA and lower baseline level of HIF2A were associated with shorter PFS; only lower baseline level of HIF2A was correlated with shorter OS. The lower expression level of DLL4 after pazopanib treatment was associated with higher response rate probability.

Conclusions

Pazopanib was clinically active and well tolerated as second-line treatment after sunitinib in mRCC patients. DLL4, VEGFA and HIF2A may be potential biomarkers of clinical efficacy in this setting (NCT:02324803).

Clinical trial identification

NCT02324803

Disclosure

All authors have declared no conflicts of interest.