For patients with metastatic renal cell carcinoma (RCC), checkpoint inhibitor therapy is the standard of care. However, if that doesn't work, vascular endothelial growth factor receptor (VEGF-R) tyrosine kinase inhibitors can be the next option, but there is no prospective data on the efficacy of these drugs for RCC in this setting. In an attempt to provide evidence for the effectiveness of VEGF-R tyrosine kinase inhibitors for RCC previously treated with immune checkpoint inhibitors, researchers conducted a phase 2 trial of the VEGF-R tyrosine kinase inhibitor axitinib in patients with metastatic RCC.
For this study, published in Lancet Oncology, the investigators enrolled 40 patients with histologically or cytologically confirmed locally recurrent or metastatic RCC with clear cell histology. To be eligible for the trial, patients had to have had prior treatment with checkpoint inhibitors, a Karnofsky Performance Status of 70% or higher, and be at least 18 years old. To begin, participants were administered 5 mg twice daily of axitinib with dose titration every 14 days in 1 mg increments, up to 10 mg twice daily as the maximum dose, as long as treatment-related adverse events didn't include grade 2 or higher mucositis, diarrhea, hand-foot syndrome, or fatigue. In the case of one or more of these side effects occurring, patients had a three-day reprieve of axitinib before the same dose was continued.
After a median follow-up of 8.7 months, median progression-free survival was 8.8 months. The most common all-grade side effects included fatigue (83%) and hypertension (75%), with hypertension being the most common grade 3 adverse event, occurring in 60% of patients.
"Individualized axitinib dosing in patients with metastatic RCC previously treated with checkpoint inhibitors did not meet the prespecified threshold for progression-free survival, but these data show that this individualized titration scheme is feasible and has robust clinical activity," conclude the study authors. "These prospective results warrant consideration of axitinib in this setting."
For More Information
Orstein MC, Pal SK, Wood LS, et al (2019). Individualized axitinib regimen for patients with metastatic renal cell carcinoma after treatment with checkpoint inhibitors: a multicenter, single-arm, phase 2 study. Lancet Oncol. [Epub ahead of print] DOI:10.1016/S1470-2045(19)30513-3
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