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LBA4511 Background: Interleukin-2 (IL2), used to treat MRCC, is not known to improve survival. To assess this potential benefit, the French Immunotherapy Intergroup designed a multicenter trial for patients (pts) with intermediate prognosis for response to cytokine treatment (Negrier et al NEJM 1998). Methods: Untreated pts with more than one metastatic site and Karnofsky score ≥80 were randomized to medroxyprogesterone (MPA: control group), α-Interferon (IFN), sc IL2 or IFN+sc IL2 in a 2x2 factorial design. Patients were evaluated after 3 months; pts without progression continued treatment for up to 6 months. The primary endpoint was overall survival (OS). The planned sample size was 456 pts based on a minimum expected difference of 10% in OS at 2 years with 5% α error and 80% power. Intent-to-treat analysis was planned 6 months after last enrollment. OS analysis (1 interaction check test and 2 log-rank tests) will be performed after α-level adjustment to maintain overall α risk at 0.05. Results: From January 00 to July 04, 492 pts were randomized: 123 to MPA, 122 to IFN, 125 to IL2 and 122 to IFN+IL2. Patient characteristics were well balanced between the groups. Median age was 61 years, 75% were males, Karnofsky score was ≥ 90 in 61%, 96% had nephrectomy, time from initial diagnosis to metastases was > 1 year in 34%. A total of 11 vs. 60 vs. 127 vs. 181 grade 3/4 toxic events were observed in the MPA, IFN, IL2 and IFN+IL2 groups, respectively; no toxic death occurred. Response rates (WHO criteria) at 3 months in the 4 groups were 2.6, 4.4, 5.1 and 10.4% respectively. Current median follow up is 28 months. OS will be analyzed in January 05. Conclusions: This study will establish whether cytokines improve OS in MRCC pts with intermediate prognosis. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche
Négrier et al. (Wed,) studied this question.