Background

Sorafenib is an orally active multikinase inhibitor which has been shown to improve progression free survival in low-risk & intermediate-risk status advanced clear-cell RCC after previous systemic therapy.

Methods

Between May 2006 and December 2010, patients with advanced RCC with either clear cell or non-clear cell histopathology who had progressed on prior systemic chemotherapy or were treatment naïve, ECOG performance status 0-2, commenced treatment with sorafenib (400 mg twice daily continuously) through an expanded access clinical trial in two tertiary centres in Sydney and Melbourne. We report the pooled outcomes of these two studies.

Results

Total 47 patients with metastatic RCC were treated with sorafenib. After median follow up of 11.7 months, the median PFS was 4.6 months. 38 patients died by the time of analysis. Overall one patient showed complete response (CR), 6 patients (13%) had partial response (PR) & 29 patients (62%) had stable disease (SD) as the best response. Eight (17%) had non-clear cell histopathology & five (10%) had sarcomatoid features. In non-clear cell cohort, 5 patients (62.5%) showed SD. 23 (49%) patients were treatment naïve; 1/23 showed CR, 5/23 had PR and 13/23 had SD (clinical benefit: 83%). Overall 14 (30%) & 22 (47%) patients had high risk status according to MSKCC & Heng prognostic scores, respectively. In MSKCC poor prognostic group, one patient had CR, 2/14 showed PR & 8/14 had SD (clinical benefit: 79%). In Heng poor prognostic group, one patient had CR, 2/22 showed PR & 13/22 had SD (clinical benefit: 73%). Sorafenib-related serious adverse events were seen in 10 patients. The most common adverse events were hand-foot syndrome (53%), rash (47%), fatigue (42%), nausea (40%) and diarrhoea (32%).

Conclusion

This study confirms the efficacy & tolerability of sorafenib in a different spectrum of advanced RCC patients including non-clear cell histology, poor prognostic status & as first line treatment.