Results from a phase 2 clinical trial suggest that individualized axitinib dosing is a feasible treatment option for patients with metastatic renal cell carcinoma (RCC) previously treated with checkpoint inhibitors (Lancet Oncol. 2019 Aug 16. Epub ahead of print).

“Axitinib is a VEGF-R inhibitor with clinical data supporting increased activity with dose titration,” said Moshe Ornstein, MD, Department of Hematology and Medical Oncology, Cleveland Clinic-Taussig Cancer Institute, Ohio,and colleagues, describing the purpose of the research.

Dr Ornstein and colleagues conducted this multi-center study to evaluate the activity of axitinib administered in an individualized dosing algorithm in patients with metastatic RCC (mRCC) previously treated with checkpoint inhibitor therapy.

A total of 40 patients were enrolled in the study between January 5, 2016, and February 21, 2018, the primary end point of which was progression-free survival.

To be eligible for enrollment, patients with mRCC had to have a Karnofsky score ≥70% and measurable disease after checkpoint inhibitor therapy. Treatment began as axitinib 5 mg twice daily, with dose titration every 14 days in 1-mg increments up to a maximum dose of 10 mg twice daily.

Patients were monitored for grade 2 adverse events (AEs), including mucositis, diarrhea, fatigue, and hand–foot syndrome. If AEs occurred, axitinib treatment was stopped for 3 days, with dose reductions made if AEs continued to occur. 

The median follow-up time frame was 8.7 months, and the median progression-free survival rate was 8.8 months (95%CI, 5.7-16.6). The most common AEs experienced by patients were fatigue (83%) and hypertension (75%). No treatment-related deaths occurred.

“Individualized axitinib dosing…did not meet the prespecified threshold for progression free survival, but these data show that this individualised titration scheme is feasible and has robust clinical activity,” concluded Dr Ornstein and colleagues, adding that these findings warrant consideration of axitinib in this setting. —Kaitlyn Manasterski