First-line mTOR inhibition in metastatic renal cell carcinoma (mRCC): An updated analysis from the International mRCC Database Consortium (IMDC).

Abstract

e15518 Background: FDA approval of the mTOR inhibitors (mTORi) in mRCC was based on efficacy in poor risk patients (pts) in the first line setting for temsirolimus (T) and in VEGF inhibitor-refractory pts for everolimus (E). Little is known about T’s effectiveness in good and intermediate risk patients and E’s outcomes in the first line setting. Methods: We interrogated the IMDC for the outcomes of pts who received mTORi as first-line targeted therapy. Results: 127 pts received a first line mTORi; the majority received T (93 T, 34 E). The main reasons for T administration were poor risk (38%), non-clear cell histology (27%), and clinical trial (15%) whereas clinical trial (82%) and non-cc histology (6%) drove E use. Of the T and E pts, 58% and 32% were poor risk, respectively. Median age was 61 years and median KPS was 80%. 68% had prior nephrectomy (62% T vs. 82% E). Median progression-free survival (PFS) and overall survival (OS) are detailed below. In the 97 pts with response data, 5% and 53% for T and 8% and 58% for E achieved partial responses and stable disease, respectively. Progressive disease as best response occurred in 41% for T and 33% for E. Second line therapy was captured in 52 pts (41%), of whom 48 received VEGF inhibitors. Conclusions: Given the different populations in which they were administered, direct comparisons of the frontline efficacy of T vs. E cannot be made. The majority of T pts were poor risk, which their dismal PFS and OS reflect. The better outcomes in the E pts highlight that the majority were not poor risk and were healthy enough for clinical trials. While limited by small numbers, this data characterizes a real world experience of mTORi in the first line setting. [Table: see text]