Renal cell carcinoma (RCC) tumors generally display specific genetic alterations that cause cancer cells to increase the metabolism of glutamine. Dual targeting of glucose and glutamine metabolism by the mTOR inhibitor everolimus, plus the glutaminase inhibitor telaglenastat, showed preclinical synergistic anticancer effects.
The Phase II ENTRATA study, led by Nizar Tannir, M.D., enrolled 69 patients with a median of three prior lines of therapy for advanced metastatic disease, including 100% with two or more prior tyrosine kinase inhibitors (TKIs), and 88% with checkpoint inhibitors. At a median follow-up of 7.5 months, median progression-free survival (PFS) was 3.8 months for the combination versus 1.9 months for the placebo.
The results from this study showed that telaglenastat plus everolimus demonstrated improvement in PFS for heavily pretreated RCC patients and warrants further assessment of glutaminase inhibitors as potential novel treatments.
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