Evaluation of axitinib to downstage cT2a renal tumours and allow partial nephrectomy: a phase II study.

Objective: To evaluate the ability of neoadjuvant axitinib to reduce the size of T2 renal cell carcinoma (RCC) for shifting from a radical nephrectomy (RN) to a partial nephrectomy (PN) indication, offering preservation of renal function.

Patients And Methods: Patients with cT2aN0NxM0 clear-cell RCC, considered not suitable for PN, were enrolled in a prospective, multicentre, phase II trial (AXIPAN). Axitinib 5 mg, and up to 7-10 mg, was administered twice daily, for 2-6 months before surgery, depending on the radiological response. The primary outcome was the number of patients receiving PN for a tumour <7 cm in size after neoadjuvant axitinib.

Results: Eighteen patients were enrolled. The median (range) tumour size and RENAL nephrometry score were 76.5  (70-98) mm and 11 (7-11), respectively. After axitinib neoadjuvant treatment, 16 tumours decreased in diameter, with a median size reduction of 17% (64.0 vs 76.5 mm; P < 0.001). The primary outcome was considered achieved in 12 patients who underwent PN for tumours <7 cm. Sixteen patients underwent PN. Axitinib was tolerated in the present study, as has been previously shown in the metastatic setting. Five patients had grade 3 adverse events. Five patients experienced Clavien III-V post-surgery complications. At 2-year follow-up, six patients had metastatic progression, and two had a recurrence.

Conclusion: Neoadjuvant axitinib in cT2 ccRCC is feasible and, even with a modest decrease in size, allowed a tumour shrinkage <7 cm in 12 cases; however, PN procedures remained complex, requiring surgical expertise with possible morbidity.