Second-line sequential therapy in patients with metastasized renal cell carcinoma (mRCC): Retrospective comparison of common treatment options following failure of receptor tyrosine kinase inhibitor therapy.

Abstract

e15059 Background: Everolimus (EV) is an efficacious treatment option after failure of receptor tyrosine kinase inhibitor (rTKI) therapy in mRCC patients. However, the best sequence of targeted therapy options has not been sufficiently defined. The objective of this study was to describe the clinical activity of sequence options in 2nd line treatment, i.e. rTKI followed by EV vs. rTkI followed by another rTKI. Methods: Retrospective study of 108 patients receiving rTKI or everolimus treatment after progression on first-line rTKI therapy at 2 German academic centres. Sequence of systemic targeted treatment consisted of an rTKI-rTKI-sequence (n=46; sunitinib-sorafenib, n= 35; sorafenib-sunitinib, n=11) or an rTKI-EV sequence (n=62). Median progression free survival (PFS) and median overall survival (OS) were determined for the two sequence treatment options using the Kaplan-Meier method. Response to treatment was assessed according response evaluation criteria in solid tumors (RECIST) 1.0. Results: Sequence treatement groups (rTKI-rTKI vs. rTKI-EV) did not significantyl differ by gender, MSKCC prognostic group, or ECOG performance status. Best response to 2nd line therapy included partial response (EV: n=2, 3%; rTKI: n=5, 11%; p=.11) and stable disease (EV: n=30, 48%; rTKI: n=15, 33%; p=.21) for a disease control rate of 51.5% (EV) and 43.4% (rTKI), respectively. The estimated 2nd line PFS was 3.6 months (92% CI: 1.8 – 5.4) for Everolimus and 4.0 months (3.2 – 4.9) for rTKI sequential therapy. The estimated OS was longer for the group of patients receiving the rTKI-EV sequence (43 months; 95% CI: 33.9 – 52.1) than for those receiving the rTKI-rTKI sequence (29 months, 95% CI: 18.6 – 39.5; p = .03). However, the rTKI-rTKI group was characterized by a relatively short first-line PFS (6.6 months compared to 10.6 months of the rTKI-EV group) which may at least in part explain the observed OS difference. Conclusions: Common sequence treatment options may have comparable efficacy in terms of PFS and response rate. The observed differences in OS await further confirmation in prospective randomized trials.