Proof of concept of correlation between progression-free survival (PFS) and overall survival (OS) in treatment-naive patients with advanced renal-cell carcinoma (mRCC): Final results of a randomized phase II study comparing sorafenib plus interleukin-2 (IL-2) versus sorafenib alone: The ROSORC trial.

Abstract

e15589 Background: The outcome analyses of the randomized phase 2 ROSORC trial, did not show any difference in terms of PFS between mRCC patients undergoing first-line treatment with sorafenib plus IL-2 versus sorafenib monotherapy (7.3 versus 6.9 months in favour of the combination arm; p= 0.109). (Procopio et al BJC 2011). Overall survival analyses are here reported. Methods: In this open-label phase 2 prospective study, 128 treatment-naïve patients with mRCC were randomized to receive either sorafenib 400 mg twice daily plus subcutaneous IL-2 4.5 MIU five times a week for 6 weeks every eight weeks (Arm A), or sorafenib alone (Arm B). The primary endpoint was PFS, while the secondary endpoint was OS. Survival analyses were evaluated by Kaplan-Meier plots and compared by two-sided log-rank test. Results: After a median follow up of 58 months (interquartile range 28-63), the median OS was 38 and 33 months in arm A and B respectively (p= 0.667). The 5-year OS was 26.3 % (95% CI: 15.9-43.5) and 23.1% (95 % CI: 13.2-40.5) in the combination and single agent arm, respectively. Overall we observed 85 deaths and among them, 42 occurred in the Arm B. Overall, 49 (74 %) and 48 (77 %) patients in the Arm A and B, respectively, received at least one targeted therapy (TT) after disease progression, including sunitinib, everolimus, axitinib or temsirolimus. Most common adverse events (AEs) included fatigue, hand-foot syndrome, hypertension and diarrhea and were mild in grade (Grade 1-2). Grade 3-4 AEs were documented in 38 % and 25 % of patients receiving combination and single agent treatment, respectively. Conclusions: While the PFS observed was in keeping with previous literature data regarding sorafenib, either as a single agent or in combination, the OS dramatically improved results reported so far in prospective randomized trials. This outcome suggests lack of correlation between PFS and OS and a synergistic effect of sequential TTs following sorafenib failure. Clinical trial information: NCT00609401.