Subgroup analysis and updated results of the randomized study comparing sorafenib (So) plus interleukin-2 (IL-2) versus So alone as first-line treatment in metastatic renal cell carcinoma (mRCC).

Abstract

4589 Background: A randomized phase II study showed that in the first line treatment of mRCC, the combination So + IL-2 moderately improves the efficacy when compared to So alone. The subgroup analysis planned in the study design and updated results are reported. Methods: One hundred twenty eight treatment-naïve patients with mRCC were enrolled in the study. Patients were randomized to receive So (given orally at 400 mg twice daily, continuously) and IL-2, 4.5 MIU subcutaneously, five time a week for four consecutive weeks every six (Arm A), or So alone (Arm B).After the first 40 patients enrolled, 20 in each arm, a dose reduction of IL -2 was performed in order to improve the safety profile. Therefore, the remaining 44 patients received IL-2 at 3 MIU for 2 consecutive weeks every four. The study sample size was calculated according to a “phase 2.5 design“ with progression free survival (PFS) as the main endpoint. PFS curves were estimated by the Kaplan-Meier method and compared by means of the one-sided log-rank test.The efficacy and safety analyses will be performed on Intent to treat population. Results: The overall median PFS was 33 weeks for So plus IL-2, compared to 28 weeks for So alone (p=0-123). The 1-year PFS was 31.6 % and 28.9 % in favour of the combination treatment. In patients with good prognosis the median and 1 year PFS were 49 weeks and 47.4 % and 41 weeks and 32.1 % in favour of the combination treatment. When considering the two subgroups of patients receiving full or lower dose of IL-2 separately, the median PFS was 44.5 weeks compared to 31 weeks in favour of the higher dose. Additionally, the 1 year PFS was 45 % and 25.1 % for full and lower dose of IL-2 respectively. The most commonly reported adverse events (AEs) were asthenia, hand foot syndrome, hypertension and diarrhoea. Grade 3-4 AEs were reported in 33% of patients in the combination treatment arm and in 22% in the single agent arm respectively. Conclusions: The combination So + IL-2 was feasible. Subgroup analysis suggest that good prognosis patients could more benefit from the addition of IL-2. The improvement in PFS was meaningful in patients receiving higher doses of IL-2. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer, Novartis, Pfizer, Roche, Wyeth