Introduction: In renal cell carcinoma (RCC), partial nephrectomy (PN) is imperatively indicated for individuals with solitary kidney, chronic kidney disease, or bilateral tumors. Neoadjuvant Tyrosine Kinase Inhibitor therapy can potentially cytoreduce renal tumors and may therefore permit PN in circumstances not otherwise feasible. We report interim analysis of the PADRES (Prior Axitinib as a Determinant of Outcome of Renal Surgery NCT03438708).
Methods: This was a single arm phase II clinical trial of neoadjuvant axitinib in patients with complex renal mass (RENAL nephrometry score 10-12 and cT1b-cT3M0) biopsy-proven clear cell RCC with strong indications for partial nephrectomy (PN), and in whom radical nephrectomy may result in dialysis dependence. Axitinib 5 mg was administered orally twice daily for 8 weeks prior to surgery. Primary outcome was reduction in longest tumor diameter based on imaging criteria; secondary outcomes included tumor response (RECIST), change in RENAL score, feasibility of PN, change in estimated glomerular filtration rate (?eGFR), post-surgical complications, and survival outcomes.
Results: 27 patients consented for study of which 26 proceeded with protocol (median age 69 years; median follow-up 12 months). Prior to therapy, 19 (73.1%) patients had = clinical T3a staged tumors. Post therapy, 17 (65.4%) patients had = T3a staged tumors, and 8/26 (31%) of patients were downstaged on imaging. Axitinib resulted in reductions in median tumor size (19%, 7.7 vs. 6.3 cm, p<0.001 and RENAL score (11 vs. 10, p <0.001); 21/26 (80.9%) had partial response, and 5/26 (19.2%) had stable disease by RECIST criteria. PN was performed in 20/26 (76.9%) with median ischemia time of 34 minutes and with 25/26 (96.8%) achieving negative margins. All radical nephrectomy patients had at =T3a tumors on final pathology. Five (19.2%) had Clavien III-IV post-surgical complications. At last follow up, median ?eGFR was 4.5 mL/min/1.73m2, 1/26 (3.8%) died due to progression, and 2/26 (7.7%) had recurrence.
Conclusions: In this interim analysis, neoadjuvant Axitnib resulted in significant reductions in tumor size and complexity, enabling partial nephrectomy in a cohort of highly complex renal masses, and with acceptable safety and functional preservation. Accrual is ongoing to reach a target of 50.
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