Phase II study of axitinib for downstaging cT2a to cT1 renal tumors for allowing partial nephrectomy (AXIPAN).

摘要

575 Background: Laparoscopic Radical nephrectomy (RN) is the current standard of care for large organ confined renal tumors while partial nephrectomy (PN) is recommended for tumor sizes up to 7 cm. PN preserves long term renal function with possible effect on overall survival. Axitinib, a potent VEGFR TKI can reduce the size of primary tumor in metastatic setting. Our primary objective was to test the ability of axitinib to reduce the size of large tumors for shifting from a RN to a PN indication. Methods: Patients with localized (cT2N0M0) RCCs were enrolled in a prospective phase II trial assessing the effect of neoadjuvant axitinib prior to surgery (PN or RN). Main inclusion criteria were: age ≥ 18, histologically proven clear cell RCC, MDRD creatinine clearance ≥ 60 ml/min, cT2a N0NxM0 tumors ( Ø> 7cm; ≤ 10 cm). Medical treatment consisted in axitinib 5 mg up to 10 mg tw/d during 2 to 6 months prior surgery according to radiological response. Results: A total of 18 patients including 11 men (61%) and 7 women (39%) with a median age of 60 yrs were enrolled. Median baseline tumor size, R.E.N.A.L. score, serum creatinine and MDRD estimated GFR were: 7.5 cm, 11, 0.8 mg/dl and 96.5 ml/min respectively. Duration of treatment was 2, 4 and 6 months in 12 (66%), 3 (17%) and 3 cases (17%), respectively. After neoadjuvant treatment median tumor size and RENAL score decreased to 5.9 cm and 10. 93 % of patients presented a decrease in maximum tumor diameter, with median size reduction of 21.7%. Out of the 17 patients who were operated, 16 (94%) underwent a PN (9 robotic and 7 open), including 84% of the cases which were performed for tumors ≤ 7cm. At 1 month from surgery, median serum creatinine and MDRD estimated GFR were 0.88 mg/dl and 88 ml/min, respectively. Medical and surgical complications rate was 11% including 1 embolization for severe bleeding and 1 Clavien V complication at 1 month after surgery due to massive myocardial infarction. Conclusions: Neoadjuvant axitinib in cT2renal tumors allowed cT1 downstaging and nephron sparing surgery in more than 80% of the cases. However, PN procedures remained high complexity cases requiring adequate surgeon expertise and information of the patients for possible morbidity of these procedures. Clinical trial information: RECF2256.