Nexavar is an orally active, multi-kinase inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced renal cell carcinoma. Nexavar has wide anti-tumor effects and has been tested in a variety of other cancers, including prostate and melanoma.In a pilot study, 6 patients with recurrent NSCLC were treated with single agent Nexavar®. This study demonstrated single agent activity with partial responses in two patients and stable disease in two others. This led to a larger study involving 52 patients with relapsed NSCLC treated with single agent Nexavar. In this study there were no partial or complete remissions, but 59% had stable disease. The median progression-free survival was 2.7 months and the overall survival was 205 days. There were no grade IV toxicities. 8% of patients in this study had bleeding. Three patients in this study had Nexavar discontinued due to hand-foot syndrome, elevated lipase and myocardial infarction. A quality of life study concluded that Nexavar did not adversely impact patient-reported outcomes in function and symptom response during treatment.
The results of a phase I clinical trial evaluated the combination of Nexavar and Iressa® (gefitinib) for the treatment of 32 patients with refractory or recurrent NSCLC were presented at the 2005 ASCO meeting. It was concluded that Nexavar and Iressa was a safe combination for treating patients with NSCLC.
In another phase I/II clinical trial, Nexavar was combined with Taxol® (paclitaxel) and Paraplatin® (carboplatin) for treatment of 15 patients with advanced progressive NSCLC. The partial response rate was 29% and 50% had stable disease for a disease control rate of 79%. The median duration of response was 25 weeks and progression-free survival was 7.5 months. There appeared to be no increase in toxicity from adding Nexavar to Taxol and Paraplatin in this study.
Recently, however, Nexavar was dropped from an ongoing trial. Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals have stopped a late stage trial of their cancer drug Nexavar (sorafenib) in patients with nonsmall-cell lung cancer (NSCLC), because it was not showing the hoped for increase in survival. The ESCAPE study was a multicentre, randomized, double-blind, placebo controlled phase 3 trial involving more than 900 NSCLC patients at over 140 clinics in North and South America, Europe and Asia.
Following a planned interim analysis, the trial’s independent data monitoring committee (DMC) concluded that the drug was not going to meet the trial’s main goal of improving overall survival.
In conclusion, although the discontinuation of Nexavar in a phase III trial throws a shadow upon its future role in lung cancer, there are several suppooting phase II trials and it should be considered supported by medical literature.
Liu B, Barrett P, Choyke K, et al. A phase II study of BAY 43-9006 (sorafenib) in patients with relapsed non-small cell lung cancer (NCLC). Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I, Vol 24, No 18S (June Supplement), 2006:abstract 17119.
Gatzemeier U, Blumenschein F, Fosella R, et al. Phase II trial of single-agent sorafenib in patients with advanced non-small cell lung carcinoma. Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I, Vol 24, No 18S (June Supplement), 2006:abstract 7002.
Gondek K, Dhanda R, Simantov R, et al. Health-related quality of life measures in advanced non-small cell lung cancer patients receiving sorafenib. Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I, Vol 24, No 18S (June Supplement), 2006:abstract 17085.
Adjei AA, Mandrekar S, Marks S, et al. A phase I study of BAY 43-9006 and gefitinib in patients with refractory or recurrent non-small cell-lung cancer (NSCLC). Journal of Clinical Oncology 2005 ASCO Annual Meeting Proceedings. Vol 23, No. 16S, Part I of II (June 1 Supplement), 2005:abstract 3067.