The evolution of debulking nephrectomy and patient characteristics in metastatic renal cell cancer patients enrolled into first-line tyrosine kinase inhibitors clinical trials.

Abstract

513 Background: The introduction of tyrosine kinase inhibitors (TKIs) revolutionized treatment of metastatic renal cell cancer (mRCC). The role of debulking nephrectomy (DN) still remains unresolved. We reviewed the rate of DN and characteristics of patients enrolled in prospective clinical trials with TKIs through and after 2007 (Motzer, N Engl J Med, 2007). Methods: PubMed, Cochrane library, ASCO and ESMO web sites were searched for phase I-III clinical trials with at least 15 patients of first line TKIs administered alone/combination for mRCC. Expanded access/randomized discontinuation trials were excluded. We used PRISMA guidelines for data collection. All trials included histology, DN, prior cytokine therapy and efficacy data. Trials missing either performance status (PS) or MSKCC criteria data were included. We reviewed 72 trials; 42 trials are included: Group 1: 22 (phase I/II-19, phase III-3) trials completed through 2007 with 2,355 patients, Group 2: 20 trials (phase I/II-17, phase III-3) completed after 2007 with 3,719 patients. Thirty trials with 1,055 patients, all phase I/II, were excluded. Group characteristics were compared using a Pearson Chi-square test at a 2-sided significance level of 0.05, median progression free survival (PFS) with available 95% CI were compared using weighted T-Test. Results: Group 2 had statistically significantly (p<0.001) less DN (85.7% vs 93.7%), less prior cytokine therapy (11.7% vs 46.8%), more poor prognosis (9.8% vs 4.0%), and intermediate prognosis characteristics (56.0% vs 51.9%), more PS 2 (2.8% vs 0.8%), and a similar rate of clear cell histology (97.9% vs 97.2%, p=0.097). Clinical objective response per intent to treat analysis was higher in Group 2 (28.6% vs 23.1%, p<0.001) with similar clinical benefit (73.2% vs 75.3%, p=0.074) and comparable PFS (median 9 vs 8.2 months, p = 0.2528). Conclusions: The use of debulking nephrectomy in patients participating in clinical trials has declined in the TKIs era. More patients with worse prognostic parameters participated in TKI trials after 2007. The reduction in prior cytokine therapy prevents estimation of these changes on TKI efficacy.