Adjuvant treatment for resected renal cell carcinoma. Are all strategies equally negative? Potential implications for trial design with targeted agents

Background: Although data from ongoing trials with targeted agents are awaited, we used a meta-analytical approach to explore whether cytokines (CK), vaccines (VAX), or other therapies may differentially influence patients′ outcomes. Materials and Methods: The objective was to determine whether significant interactions exist according to treatment (CK vs. VAX vs. other), in the context of a literature-based meta-analysis. Fourteen trials (3380 patients) were identified, with 10 randomized clinical trials (RCTs) (2257 patients) providing data for the primary outcome - 5-year relapse-free survival (RFS). The primary selected end point was 5-year RFS; secondary end points were 5- and 2-year overall survival (OS) and 2-year RFS. Event-based relative risk (RR) ratios with 95% confidence intervals (CI) were extracted and cumulated according to a random-effect model from articles/presentations. Testing for heterogeneity was performed as well. Results: Although not statistically significant, an effect in favor of a qualitative interaction according to treatment was found for 5-year RFS, with a likely detrimental effect in CK (P =.42) in contrast to that found in VAX subpopulation (P =.76). For the secondary end points, a similar effect in favor of a quantitative significant interaction according to treatment was found for 5-year OS, regardless of the approach adopted, with a different magnitude of treatment effect. In addition, a borderline significant (P =.05) detrimental effect in terms of 2-year OS against the use of adjuvant treatment was determined in the CK subpopulation (RR, 1.24; 95% CI, 0.99, 1.54). Conclusion: The effect in favor of a qualitative interaction according to the adopted strategy is intriguing and suggests potential implications for trial design with targeted agents.