How are mTOR inhibitors applied in metastatic RCC?
Two mTOR inhibitors, everolimus and temsirolimus, have been approved for use in metastatic RCC. Everolimus was compared to placebo in a phase III study including patients who were refractory to sunitinib and/or sorafenib. In this study, everolimus therapy was associated with an improvement in PFS. As such, everolimus has been approved for use after failure of VEGF tyrosine kinase inhibitor therapy. In a randomized, phase II experience, the combination of lenvatinib and everolimus showed superiority over everolimus alone. For this reason, this combination may supplant everolimus monotherapy in the previously treated setting. In contrast, temsirolimus was approved based on a study comparing temsirolimus, IFN-γ, and the combination of agents in patients with poor risk metastatic RCC. In the context of this study, poor risk was defined as having ≥3 of the following predictors of short survival:
- • LDH > 1.5 × the upper limit of normal
- • Hemoglobin < lower limit of normal
- • Corrected serum calcium >10 mg/dL
- • Interval of <1 year from original diagnosis to the start of systemic therapy
- • Karnofsky performance score <70, and (6) ≥2 sites of organ metastases.
Among the three treatment arms, temsirolimus was associated with improved overall survival. Considering this data, temsirolimus has been approved for the first-line treatment of poor-risk metastatic RCC.
