Commentary on Randomized phase II trial of first-line treatment with sorafenib vs. interferonα-2a in patients with metastatic renal cell carcinoma: Escudier B, Szczylik C, Hutson TE, Demkow T, Staehler M, Rolland F, Negrier S, Laferriere N, Scheuring UJ,

An open-label, phase II study to evaluate progression-free survival (PFS), overall best response, adverse events (AEs), and patient-reported outcomes with sorafenib vs. interferonα-2a (IFNα-2a) in patients with untreated, advanced renal cancer. l of 189 patients were randomly assigned to oral sorafenib 400 mg twice daily or to subcutaneous IFNα-2a 9 million U three times weekly (period 1). Sorafenib patients who progressed were dose-escalated to 600 mg twice daily; IFNα-2a patients who progressed were switched to sorafenib 400 mg twice daily (period 2). iod 1, PFS was similar for sorafenib-treated (n = 97; 5.7 months) and IFNα-2a-treated patients (n = 92; 5.6 months); more sorafenib-treated patients had tumor shrinkage (68.2% vs. 39.0%). Common drug-related AEs (grades ≥ 3) for sorafenib were hand-foot skin reaction (11.3%), diarrhea (6.2%), and rash/desquamation (6.2%); for IFNα-2a, these were fatigue (10.0%), nausea (3.3%), flu-like syndrome (2.2%), and anorexia (2.2%). Sorafenib-treated patients reported fewer symptoms, better quality of life (QOL), and greater treatment satisfaction. In period 2, 41.9% of patients who received sorafenib 600 mg twice daily (n = 43) experienced tumor reduction (median PFS, 3.6 months). After the switch to sorafenib 400 mg twice daily, tumors were reduced in 76.2% of 50 patients (median PFS, 5.3 months). AEs were mostly grades 1 to 2; no increase in AEs of grades ≥ 3 occurred after sorafenib dose escalation. s study, sorafenib resulted in similar PFS as IFNα-2a in patients with untreated RCC. However, sorafenib-treated patients experienced greater rates of tumor size reduction, better QOL, and improved tolerability. Both dose escalation of sorafenib after progression and a switch to sorafenib after progression on IFNα-2a resulted in clinical benefit.