Erlotinib with sirolimus for advanced renal cell carcinoma: Preliminary efficacy results

Abstract

e16037 Background: The mammalian target of rapamycin (mTOR) is an important therapeutic target in the treatment of renal cell carcinoma (RCC). Temsirolimus, an analog of rapamycin, prolongs survival when used to treat high-risk RCC patients and is approved for the treatment of advanced RCC. Oral rapamycin (sirolimus/Rapamune) is less expensive than temsirolimus and plasma levels can be routinely monitored. Pre-clinical data indicate that the combined inhibition of the epidermal growth factor receptor (EGFR) and mTOR results in enhanced anti-cancer activity, especially in cell lines with wt-VHL. Methods: All patients on this study had metastatic or unresectable renal cell carcinoma with progression despite sunitinib and/or sorafenib. Treatment was started with erlotinib (Tarceva) 150 mg po daily. On day 8, sirolimus was begun with a single 6 mg loading dose and then given as 2 mg daily. Radiographic assessments were performed every 8 weeks. Results: The current data set was obtained through July of 2008. Enrollment started in July of 2006 with the last patient accrued in March 2008; 25 patients have been treated. The median subject age was 60 years with an average of 2.6 previous medical treatments. The unconfirmed median progression free survival (PFS) was 12 weeks (range 2–52) with 4 patients remaining on active treatment and included in this analysis. No confirmed complete or partial responses were observed, but meaningful stable disease (SD) (e.g., > 6 months) was noted in a small group of patients. The most common adverse events were rash and diarrhea with the majority of these observed as a grade 1 event. Grade 3 and 4 toxicities included rash, mucositis, neurological motor weakness, dehydration, worsening cardiac function, non-ST elevation MI, and anemia. Additional efficacy, toxicity and pharmacokinetic data will be presented. Conclusions: The combination of erlotinib and sirolimus produces a median PFS of 12 weeks in a significantly pretreated RCC population, which is not dissimilar to recent results with other mTOR inhibitors in this setting. The toxicity profile of this combination is consistent with the expectations of this pre-treated patient population with advanced RCC. [Table: see text]