Is intravenous (iv) IL2 superior to subcutaneous (sc) IL2 in good prognosis patients (pts) with metastatic renal cell carcinoma (MRCC) receiving a combination of IL2 and alpha interferon (IFN)? Results of the prospective randomized PERCY Duo trial

Abstract

4536 Background: Pts with a single metastatic site are more likely to benefit from an IL2 and IFN combination (Negrier NEJM 1998). The French Immunotherapy Intergroup designed a multicenter trial to assess the potential benefit of iv over sc IL2 in IL2+IFN combination in this subgroup. Methods: Untreated pts, Karnofsky score ≥ 90 and a single metastatic site were randomized into this 2 arm trial. Pts received continuous IL2 infusion (18 million IU/m2/d) (arm A), or sc IL2 injections (9 or 18 million IU) twice daily (arm B). IFN was given sc (6 million IU) 3d/week in both arms. Tumor responses (OMS criteria) were assessed at weeks 12 and 27. The primary endpoint was overall survival (OS), with an expected difference of 15% at 4 yrs in favor of iv IL2. The planned sample size was 220 to have 80% power at 5% significance level with a one-sided test. One intent-to-treat analysis was performed and survivals were compared using log-rank tests. Results: From January 00 to January 05, 80 and 75 pts were randomized to arms A and B respectively. Enrollment was stopped early due to low accrual; analysis was performed at 40-month median follow up. Patient characteristics were well balanced between groups. Median age was 55, 82% pts were male, 68% had lung metastases, and 37% had more than 1 year from renal tumor to metastases. No toxic death occurred, gr 3/4 vomiting, rise in creatinine level, hypotension and neurologic toxicity were significantly higher in arm A. Response rates were 17.9 vs 21.3%, in arms A and B, respectively. Progression-free survivals were not significantly different (P: 0.285). The difference in OS was not significant: median 37.7 months [95%CI: 28.2–58.4] with iv IL2 vs. 26.3 [95%CI: 24.5–34.2] with sc IL2 (P: 0.127). Conclusions: Iv IL2 combined with IFN confers no significant advantage over a sc IL2 combination in selected pts with good prognosis MRCC. Since some toxicities were significantly more frequent with iv IL2, the use of this combination cannot be recommended. Because of premature stop, the trend in favor of iv IL2 should encourage further studies before final conclusions can be drawn. [Table: see text]