Pre-Op Axitinib Helps for Partial Nephrectomy of Complex Renal Tumors

SAN DIEGO -- Use of neoadjuvant axitinib (Inlyta) resulted in significant reductions in tumor size and complexity, enabling partial nephrectomy in a cohort of patients with highly complex renal masses in whom the procedure would ordinarily not be feasible, according to an interim analysis from a small phase II trial.

A course of the tyrosine kinase inhibitor prior to surgery resulted in reductions in median tumor size (7.7 vs 6.3 cm, P<0.001) and RENAL nephrometry score (11 vs 10, P<0.001), reported Kevin Hakimi, BS, a medical student at the University of California San Diego School of Medicine, in a presentation at the Society of Urologic Oncology annual meeting.

In addition, "19 of 26 patients were able to undergo partial nephrectomy," Hakimi told MedPage Today. "For patients that have large masses that have imperative indications for partial nephrectomy -- such as a decreased eGFR [estimated glomerular filtration rate] or some other indication that would make them dialysis dependent if they underwent a radical nephrectomy -- using a neoadjuvant approach can make them amenable to a partial nephrectomy and allow them to conserve more renal function and avoid dialysis dependence or some other complication from chronic kidney disease."

The results are based on an analysis of patients with complex biopsy-proven clear cell renal cell carcinoma in the single-arm PADRES (Prior Axitinib as a Determinant of Outcome of Renal Surgery) trial. All 26 patients had strong indications for partial nephrectomy, including an eGFR <60 (suggesting chronic kidney disease), or a solitary kidney. Thus, Hakimi explained, these patients faced the risk of dialysis dependence if they underwent radical nephrectomy.

Patients had a median age of 69 years and a median follow-up of 12 months. Axitinib was administered at a dose of 5 mg orally twice daily for 8 weeks prior to surgery. The primary outcome was reduction in longest tumor diameter based on imaging criteria and achievement of partial nephrectomy. Secondary outcomes included change in tumor diameter, RENAL nephrometry score, renal function based on eGFR, tumor response, and surgical complications.

In addition to reductions in tumor size and RENAL scores, Hakimi and his colleagues reported that 34.6% of patients had a partial response to treatment, 65.4% achieved stable disease, 34.6% had tumors downstaged on imaging, and 92.3% achieved negative margins.

Six of the 26 patients had Clavien grade III-IV surgical complications after partial nephrectomy, including urine leaks in four patients.

The most common postoperative adverse events were fatigue (low grade in 34.6%, high grade in 3.8%) and hypertension (low grade in 38.5%, high grade in 11.5%).

"Looking at renal functional outcomes at the 1-month mark, renal function outcomes were preserved pretty well," Hakimi said. "Only two patients had a greater than 50% reduction in their eGFR, and only one patient was dialysis dependent, and that patient underwent a radical nephrectomy."

"So we showed that in this complex cohort of patients, axitinib can be used to cytoreduce masses and enable partial nephrectomy in a highly specific cohort of patients with imperative indications for the procedure," Hakimi concluded, adding that accrual for the trial is ongoing, with a targeted enrollment of 5o patients.

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