Angiogenesis inhibitor therapies for metastatic renal cell carcinoma: effectiveness, safety and treatment patterns in clinical practice-based on medical chart review.

OBJECTIVE: To assess the effectiveness, safety, and treatment patterns of anti-angiogenic agents in metastatic renal cell carcinoma (mRCC) in tertiary clinical practice settings. PATIENTS AND METHODS: We retrospectively reviewed the medical records in two tertiary oncology centres in the USA for all patients treated while off clinical trials from April 2003 to June 2008 who met the entry criteria and received one or more prescriptions for sunitinib or sorafenib, or one or more intravenous administrations of bevacizumab (off-label) as first-line anti-angiogenic treatment. The objective response rate (ORR) reviewed by independent physicians, adverse events (AEs), and treatment modifications were assessed. RESULTS: Among 144 patients receiving sunitinib (57), sorafenib (62) and bevacizumab (25), the median treatment duration was 10.5, 8.1 and 7.9 months, and the ORR was 37%, 9% and 13%, respectively. The ORR was lower for patients with metastases to bone, brain, lungs or lymph nodes. Common AEs (all grades) for sunitinib were fatigue (53%), diarrhoea (37%); for sorafenib, diarrhoea (50%), fatigue (40%); for bevacizumab, fatigue (40%), nausea (24%). In all, 34 (60%), 51 (82%) and 20 (80%) patients receiving sunitinib, sorafenib and bevacizumab, respectively, discontinued treatment; 10 (18%), 11 (18%) and four (16%) discontinued due to AEs; 21%, 40% and 12% had a dose interruption, and 30%, 35% and 0% had a dose reduction. CONCLUSIONS: Currently available anti-angiogenic agents had considerable effectiveness in clinical practice. However, the response rates appeared to be low in certain subgroups, but sample sizes were small. Patients had significant rates of AEs, many of which led to treatment modifications. The findings from this retrospective study suggest that there is a need for better-tolerated therapies for mRCC.

Predicting outcome to VEGF-targeted therapy in metastatic clear-cell renal cell carcinoma: data from recent studies.

Attempts to predict outcome in patients with metastatic clear-cell renal cell carcinoma (RCC) have conventionally been based on pretherapy clinical factors such as performance status, disease-free interval, number of metastatic sites and several laboratory variables. These factors were developed before the era of VEGF-targeted therapy. Recent analysis from trials with anti-VEGF agents indicate that these factors continue to be of major importance in patient prognostication. Additionally, several serum and molecular markers, many of which relate to certain alterations of the von Hippel-Lindau pathway, are currently being investigated. Responses to VEGF-targeted agents appear to be related to a greater modulation of serum VEGF and soluble VEGF receptor levels. The impact of von Hippel-Lindau gene status on response to VEGF-targeted therapy was tested in a large study and was not found to predict a higher response rate to these agents. However, a subset of von Hippel-Lindau mutations that predict a 'loss of function' of the von Hippel-Lindau gene seem to have the best response to these agents. Future prognostic models will incorporate molecular markers with clinical variables to refine prognosis and prediction in metastatic clear-cell RCC patients treated with novel VEGF-targeted agents. These models, if externally and prospectively validated, will culminate in the rational selection of patients for specific VEGF-directed therapeutics.