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

Abstract

Study Type – Therapy (retrospective cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Various targeted agents with differing mechanisms of action and toxicity profiles have now been approved for the treatment of advanced RCC. However, the optimal use of these agents remains a challenge. Since the approval of sorafenib and sunitinib, many patients have been treated with these two tyrosine kinase inhibitors (TKIs) in sequence, with current evidence suggesting that this approach is associated with continued clinical benefit, with limited or no cross‐resistance between the two agents. The mammalian target of rapamycin (mTOR) inhibitor, everolimus, has been shown to be as effective after two TKIs as it is after one TKI, emphasizing the importance of understanding the optimal TKI sequence before switching to an mTOR inhibitor, to provide patients with the longest progression‐free survival (PFS) benefit. This retrospective analysis of 189 patients treated sequentially with sorafenib (800 mg/day) and sunitinib (50 mg/day; 4 weeks on 2 weeks off) showed that initial therapy with either agent was associated with similar PFS benefits (median PFS 8.4 months [sorafenib] vs 7.8 months [sunitinib]; HR 1.05, 95% CI 0.78–1.40; P = 0.758). However, patients treated with sorafenib followed by sunitinib (SoSu) appeared to derive a greater PFS benefit than those treated with SuSo (median PFS with second TKI: 7.9 months [SoSu] vs 4.2 months [SuSo]; HR 0.54, 95% CI 0.39–0.74; P < 0.001). Consistent with previous studies, these findings suggest that sequential TKI therapy is associated with continued clinical benefit and that SoSu may result in a longer PFS than SuSo. 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 ...

Comparative Efficacy of Sunitinib versus Sorafenib as First-Line Treatment for Patients with Metastatic Renal Cell Carcinoma

“…As several agents showed efficacy in the treatment of mRCC, not only the first-line treatment, but also subsequent therapies are important. Porta et al [22] reported limited cross-resistance between sorafenib and sunitinib, and showed that sorafenib treatment followed by sunitinib may result in longer combined PFS than sunitinib treatment followed by sorafenib in 189 patients with mRCC. In addition, in an observational study of 145 mRCC patients that showed considerable side effects of VEGF TKIs, only 17.6% of the patients treated with sunitinib as first-line treatment could receive a second-line treatment, whereas 38.3% of the patients treated first with sorafenib could receive second-line treatment [23].…”

Prognostic Value of Hematologic Parameters in Patients with Metastatic Renal Cell Carcinoma Using Tyrosine Kinase Inhibitors

“…Several studies have demonstrated the efficacy of VEGF-targeted agents in previously untreated patients with advanced or metastatic RCC and patients with RCC who have progressed after prior therapy (Motzer et al, 2007;Sternberg et al, 2010). Clinical efficacy has been reported for these agents associated with a median overall survival (OS) of 22.9-26.4 months, PFS of 8-9 months for sunitinib or sorafenib in first line treatment (Al-Marrawi et al, 2010;Motzer et al, 2011;Porta et al, 2011). Otherhand, patients with metastatic RCC and progression on first-line cytokine therapy median time to progression was 8.7 months with sunitinib (Motzer et al, 2006).…”

Optimal first-line and second-line treatments for metastatic renal cell carcinoma: current evidence

“…[21][22][23][24] In those series, median progression-free survival on first-line sunitinib ranged from 5.1 to 8.6 months. The median progression-free survival on secondline sorafenib ranged from 2.9 to 8.9 months.…”