Progression on Everolimus

George Yaghmour

Jul 15, 2015

The NCCN Kidney cancer panel considers Everolimus and Axitinib categories 1 for Subsequent therapy for patients with mRCC clear cell predominance especially after TKI therapy. According to the RECORD 1 trial (Everoimus), and phase III (AXIS) Study (Axitinib).	 
Both Everolimus and Axitinib undergoes extensive hepatic metabolism, as they are a CYP3A4 substrate.  Oxcarbazapine is a CYP3A4 inducer and will decrease the level or effect of Everolimus, and Axitinib oral, primarily through the CYP3A4 isoenzyme. 
Efficacy and safety of temsirolimus were demonstrated at a second interim analysis of the ARCC trial, a phase III study in previously untreated patients with advanced RCC and considered as a category 1 recommendation for first-line treatment of poor-risk patients predominantly clear cell stage IV renal carcinoma. 
The NCCN Panel considers temsirolimus as category 2B recommendation after a TKI according to phase III trial (INTORSECT) comparing the efficacy of temsirolimus to sorafenib following first-line sunitinib as a treatment for patients with RCC, on top of that Temsirulimus is also a CYP3A4 substrate. 
Other TKI like Sorafinib and Sunitinib also undergoes extensive hepatic metabolism, as they are a CYP3A4 substrates and are both are category 2 A recommendation.  Bevacizumab is a category 2B recommendation after a TKI according to phase II trial. 
Everolimus treatment associated with common adverse effects,  more than 30-50% of anemia, hyperglycemia, hypercholesterolemia, mucositis, fatigue, and rash. 
In this case obviously the patient is not getting the adequate dose, and switching the Anti-seizure medication is the important point to consider in this situation. Would still consider after stopping the Oxcarbazapine to either continue the Everolimus, or Axitinib which would be reasonable choice. Would also consider clinical trial  or PD1/PDL1 according to molecular and genetics testings. Avastin, Temserolimus and other TKIs are resonable options if progressed further.