Sequential use of sorafenib and sunitinib in advanced renal-cell carcinoma (RCC): an Italian multicentre retrospective analysis of 189 patient cases.

Objective: •To conduct a retrospective, multicentre, cohort analysis to assess the sequential use of the tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib.

Patients And Methods: •Records of 189 patients with renal-cell carcinoma (RCC) who were treated with sorafenib and sunitinib sequentially between March 2004 and April 2009 at 12 Italian study centres were analysed. •Patients were treated under European Expanded Access Programmes or, following market approval, in general clinical practice. •Interventions were sorafenib (800 mg/day) and sunitinib (50 mg every day; 4 weeks on and 2 weeks off). •Progression-free survival (PFS) during treatment with the first and second TKI was evaluated.

Results: •In all, 99 patients were treated with sunitinib followed by sorafenib (SuSo) and 90 were treated with sorafenib followed by sunitinib (SoSu); 104 (55%) patients had received prior systemic therapy, mostly with cytokines. •The median (range) PFS on the first TKI was similar between treatment groups [sorafenib 8.4 (1.1-28.9) months; sunitinib 7.8 (0.5-30.4) months; hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.78-1.40, P=0.758]. Multivariate analysis showed that good Memorial Sloan-Kettering Cancer Center status was associated with increased PFS. •After the second TKI, patients in the SoSu group had a longer median PFS than those in the SuSo group (7.9 months vs 4.2 months, respectively; HR 0.54, 95% CI 0.39-0.74, P<0.001). •Multivariate analysis showed only treatment and Eastern Cooperative Oncology Group performance status (and not age, gender, study centre or previous treatment) were significantly associated with duration of PFS.

Conclusion: •Our findings suggest a limited cross-resistance between sorafenib and sunitinib and that the sequence SoSu may result in a longer combined PFS than SuSo. This is the largest retrospective study to date, though its findings are limited in part by the retrospective nature.