Sorafenib Treatment of Advanced Renal Cell Carcinoma Patients in Daily Practice: The Large International PREDICT Study

Abstract

This large, prospective, noninterventional study assessed the efficacy and safety of sorafenib in patients with advanced renal cell carcinoma (RCC) in a clinical practice setting. Sorafenib was generally well tolerated, with no unexpected adverse events observed, and provided clinical benefit in this diverse patient population. Background: Patients with advanced renal cell carcinoma in routine clinical practice can differ considerably from those in phase III studies. Patients and Methods: PREDICT (Patient characteristics in REnal cell carcinoma and Daily practICe Treatment with sorafenib) was a prospective, noninterventional study of open-label sorafenib for the treatment of advanced RCC conducted in 18 countries. Patient characteristics, therapy duration, tumor status, and tolerability were assessed at baseline and during routine follow-up. Results: Overall, 2599 patients were evaluable for safety and 2311 for efficacy. The diverse population included patients with brain metastases (5%), non-clear-cell histologies (17%), high Memorial Sloan-Kettering Cancer Center risk score (11%), poor Eastern Cooperative Oncology Group performance status (PS ! 2, 29%), and patients with no previous nephrectomy (16%) or no previous systemic therapy (37%). The median duration of sorafenib therapy was 7.3 months and was similar in clinically relevant subgroups (eg, patients with PS 2, brain metastases, or concomitant hypertension or diabetes [range, 6.7-7.0 months]). The median duration of therapy was shorter for patients with PS 3 or non-clear-cell histologies (4.6 and 4.8 months, respectively). The most common drug-related adverse events were handefoot skin reaction (20%), diarrhea (17%), and rash (8%). Conclusion: Sorafenib was generally well tolerated and provided clinical benefit in a large, diverse population of patients with advanced RCC treated in routine clinical practice.

Does dose modification affect efficacy of first-line pazopanib in metastatic renal cell carcinoma?

“…The most common AEs observed in our study were fatigue (33.3%), nausea (17.4%), diarrhea (16%), and hypertension (13%), which is consistent with data in the literature [2]. Treatment duration and toxicity data from real-world experience with sunitinib and sorafenib show that, overall, about half of patients require a dose reduction of sunitinib [13] and sorafenib [14,15] because of toxicity; however, no similar data are yet available for pazopanib. The disease control rate (DCR) in our report (n = 20; 29%) is slightly lower than that reported in the literature, but it raised significantly when considering the DCR reported in group 1 (44%).…”

Role of interleukin-6 in cancer progression and therapeutic resistance

“…All these approaches evaluated in experimental models and reached clinical trials are summarized in Table 1. [191] Breast cancer Sorafenib [192] Advanced renal cell carcinoma Sorafenib [193] Colorectal cancer Sorafenib [194] Antibodies targeting IL-6 or IL-6 signalling have been extensively investigated in experimental tumour models and clinical trials for a variety of cancers. Elsilimomab (BE-8), a murine monoclonal antibody, and siltuximab (CNTO 328), a chimeric antibody with strong affinity to IL-6 and licenced for the treatment of Castleman's disease, are used for the treatment of prostate cancer, ovarian cancer, renal cell carcinoma and colorectal cancer in combination with other chemotherapeutics [3,6,166].…”

Influence of Tyrosine Kinase Inhibitors on Hypertension and Nephrotoxicity in Metastatic Renal Cell Cancer Patients

“…Hypertension of any grade according to CTCAE was reported with an incidence ranging from 17% to 49.6% in the reviewed randomized controlled trials (Table 2) [5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22]. …”