Bevacizumab plus interferon-alpha versus interferon-alpha monotherapy in patients with metastatic renal cell carcinoma: Results of overall survival for CALGB 90206.

LBA5019 Background: Bevacizumab (BEV) plus interferon alpha (IFN) demonstrated a superior objective response rate and progression-free survival (PFS) versus IFN monotherapy in renal cell carcinoma (RCC) patients in 2 phase III trials. The primary objective of CALGB 90206 was to compare overall survival (OS) for advanced RCC patients receiving BEV plus IFN or IFN alone. METHODS: Patients with previously-untreated, metastatic RCC with a clear cell component and Karnofsky performance status of ≥ 70% were eligible. Patients were prospectively randomized to receive BEV (10 mg/kg intravenously every 2 weeks) plus IFN (9 million units subcutaneously three times weekly) or the same dose and schedule of IFN as monotherapy. Randomization was stratified by nephrectomy status and number of MSKCC adverse features. The primary endpoint was OS, defined as the time from randomization to death due to any cause. The trial was designed with 86% power to detect a hazard ratio (HR) of 0.76, assuming a two-sided type I error of 0.05. The primary analysis was an intent-to-treat approach using the stratified log-rank statistic, and the present analysis was based on the target number of 588 deaths. RESULTS: Between October 2003 and July 2005, 732 patients were enrolled; 369 pts to BEV plus IFN and 363 pts to IFN monotherapy. The median duration of follow up among censored patients was 46.2 months (IQR=45.2-48.2). The median OS was 18.3 months (95% CI; 16.5-22.5) for BEV plus IFN and 17.4 months (95% CI; 14.4-20.0, unstratified log rank p = 0.097) for IFN monotherapy. The stratified HR was 0.86 (95% CI; 0.73-1.01) for BEV plus IFN compared to IFN (stratified log-rank p = 0.069). The median OS for BEV plus IFN versus IFN was 32.5 vs. 33.5 months (p = 0.524) for MSKCC good risk, 17.7 vs. 16.1 months (p = 0.174) for intermediate risk and 6.6 vs. 5.7 months (p = 0.245) for poor risk patients. The median PFS was 8.4 months vs. 4.9 months (p<0.0001). Fifty-three percent of patients received subsequent systemic therapy. CONCLUSIONS: The addition of BEV to IFN significantly improves the objective response rate and PFS versus IFN monotherapy. Overall survival favored the BEV plus IFN arm, not meeting pre-defined criteria for significance. [Table: see text].

Duke Scholars

Author Susan Halabi Biostatistics & Bioinformatics, Division of Biostatistics