Τρίτη, 29 Μαρτίου 2016

PI3K INHIBITOR LESS EFFECTIVE THAN EVEROLIMUS FOR RENAL CANCER

As reported in the Journal of Clinical Oncology by Powles et al, the dual PI3K/mTOR inhibitor apitolisib was inferior to the mTOR inhibitor everolimus (Afinitor) in progression-free survival in a phase II trial in patients with metastatic clear cell renal cell carcinoma progressing on or after vascular endothelial growth factor (VEGF) inhibitor therapy.   
Progression-Free Survival
In the open-label trial, 85 patients from sites in the United States and Europe were randomized to receive apitolisib at 40 mg (n = 42) or everolimus at 10 mg (n = 43) once daily.  After 67 events, at a median follow-up of 16.6 months, median progression-free survival was 3.7 months in the apitolisib group vs 6.1 months in the everolimus group (hazard ratio [HR] = 2.12, P < .01). Median overall survival was 16.5 vs 22.8 months (HR  = 1.77, P = .06). The objective response rate was 7.1% vs 11.6%.
Toxicity
Grade ≥ 3 adverse events were more common in the apitolisib group (74% vs 44%), including a higher incidence of rash (24% vs 2%) and hyperglycemia (40% vs 9%). Adverse events led to discontinuation of treatment in 31% vs 12%.
A retrospective biomarker analysis indicated that VHL mutation was associated with greater progression-free survival with everolimus but not with apitolisib and that high hypoxia-inducible factor 1a protein expression was associated with better outcome in both groups.
The investigators concluded: “This study demonstrated that dual PI3K/mTOR inhibition by apitolisib was less effective than was everolimus in [metastatic] RCC, likely because full blockade of PI3K/mTOR signaling resulted in multiple on-target adverse events. VHL mutation and hypoxia-inducible factor 1a expression may be predictive of an mTOR inhibitor benefit, although prospective validation is required.”
The study was supported by Genentech.
Thomas Powles, MD, of Queen Mary University of London, is the corresponding author of the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.

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