Sunitinib still first-line therapy for metastatic renal cancer

Abstract

Everolimus (an mTOR inhibitor) does not yield better results compared with sunitinib (a VEGFR tyrosine kinase inhibitor) as fi rst-line therapy in patients with metastatic renal-cell carcinoma, new research suggests. Cross-study comparisons suggests that there are diff erent toxicity profi les between everolimus and sunitinib, indicating better tolerability of everolimus. Robert Motzer (Memorial Sloan-Kettering Cancer Center, NY, USA) and colleagues did a multicentre, randomised phase 2 trial in patients with metastatic renal-cell carcinoma to compare effi cacy and safety of everolimus and sunitinib in fi rst-line therapy, and the sequence of everolimus followed by sunitinib at progression compared with the standard sequence of sunitinib followed by everolimus. 471 patients were enrolled in the trial, of whom 238 were randomly assigned to receive fi rst-line everolimus followed by sunitinib, and 233 were randomly assigned to receive fi rst-line sunitinib followed by everolimus. After treatment, median progression-free survival was 7·9 months for fi rst-line everolimus and 10·7 months for fi rst-line sunitinib (hazard ratio [HR] 1·4; 95% CI 1·2–1·8). The researchers noted that for everolimus followed by sunitinib, the median combined progression-free survival was 21·1 months, compared with 25·8 months for sunitinib followed by everolimus (HR 1·3; 95% CI 0·9–1·7). For everolimus followed by sunitinib, median overall survival was 22·4 months compared with 32·0 months for sunitinib followed by everolimus (HR 1·2; 95% CI 0·9–1·6). However, fi rst-line sunitinib resulted in slightly higher rates of treatment-emergent adverse events than did fi rst-line everolimus, including stomatitis (57% vs 53%), fatigue (51% vs 45%) and diarrhoea (57% vs 38%). Motzer commented, “In the fi rstline setting, in this population of patients with metastatic renal-cell carcinoma, sunitinib showed higher effi cacy com pared to everolimus”. He suggested, “Everolimus use [should be] reserved for patients who progressed on sunitinib”. However, Masahiro Nozawa (Kinki University Faculty of Medicine, OsakaSayama, Japan) comments, “Seven agents are available for metastatic renal-cell carcinoma treatment at the moment: axitinib, bevacizumab, everolimus, pazopanib, sorafenib, sunitinib, and temsirolimus. Using all these agents thoughtfully can bring in better outcome from therapy.”