PL 20. The efficacy and safety of Sunitinib in first-line treatment of metastatic renal clear cell carcinoma (mRCC): A single center 34 cases report

The tyrosine kinase inhibitors (TKIs) sunitinib target the vascular endothelial growth factor (VEGF) pathway, is the first targeted agent to be approved for the first line treatment of metastatic RCC. The objective of this study was to investigate the efficacy and safety of Sunitinib in treating metastatic clear-cell RCC and to confirm if hypertension is an effective predictive factor.

A total of 36 patients with metastatic RCC were enrolled between June 2008 and Dec 2010.Among them 29 cases were first line therapy and 7 cases were in progression on first-line cytokine or sorafinib therapy. The pathology of all patients was confirmed predominant in clear cell type. Sunitinib monotherapy was administered in repeated 6-week cycles of daily oral therapy for 4 weeks, followed by 2 weeks off in 34 patients; and 3 patients were administered with 37.5 mg Qd continuously until disease progression or unacceptable toxicities occurred. Overall response rate and safety were evaluated. Hypertension is defined as a repeatedly (at least twice) elevated BP, with a systolic pressure >140 mmHg and/or a diastolic pressure >90 mmHg. We divided patients into Group A and Group B according to blood pressure level.

The median follow-up was 15 months (10 cycles), range 1.5-30 months (1 - 20 cycles). 29.4% (10/34) of the patients achieved partial responses (PR); 67.6% (23/34) of the patients demonstrated stable disease (SD) lasting ≥2 cycles. 17 (50%) patients developed progressive disease (PD) during follow-up. The median PFS is 15 (range, 3-28.5) months. A total of 9 patients died; the overall survival has not been reached; the median survival time of the deceased patients was 13 (7-24) months. The most common adverse events (AEs) were hand-foot syndrome (77.8%), thrombocytopenia (75%), hypertension (61.1%) and diarrhea (46%). Most AEs were reversible by treatment interruption. 22 (61.1%) patients developed hypertension; hypertension was associated with a long time to disease progression and long overall survival (P=.004, .000, respectively).

The results of this study demonstrate the efficacy and manageable adverse event profile of Sunitinib as a single agent in first- or second-line therapy for patients with metastatic clear cell RCC. Further, Sunitinib-associated hypertension may be a strong predictive marker for treatment efficacy in metastatic RCC.