In a phase II study reported in The Lancet Oncology, Ornstein et al found that individualized axitinib regimens showed activity in patients with locally recurrent or metastatic renal cell carcinoma who had previously received immune checkpoint inhibitor therapy, although the progression-free survival endpoint of the study was not met.
Study Details
The multicenter study enrolled 40 patients between January 2016 and February 2018 who had received checkpoint inhibitor therapy as their most recent treatment. Patients received axitinib at a starting dose of 5 mg twice daily with dose titration every 14 days in 1 mg increments up to 10 mg twice daily if there was no axitinib-related grade ≥ 2 mucositis, diarrhea, hand-foot syndrome, or fatigue. If grade 2 events occurred, axitinib was withheld for 3 days before the same dose was resumed. The axitinib dose was reduced if grade 2 events recurred, or if grade 3 or 4 adverse events occurred.
"Individualized axitinib dosing in patients with metastatic renal cell carcinoma 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."— Ornstein et al
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The primary outcome was progression-free survival. The goal was a 45% increase in median progression-free survival compared with historical data to a target duration of 9.5 months (determined by investigators to represent a clinically meaningful improvement).
Progression-Free Survival
Median follow-up was 8.7 months. Median progression-free survival was 8.8 months, which failed to meet the threshold for improvement. Objective response was observed in 18 patients (45%), with an additional 18 (45%) having stable disease. Among responders, 12 patients (67%) had responses of longer than 12 months. Most responders (n = 14) had received previous VEGF-targeted therapy.
Adverse Events
The most common adverse events of any grade were fatigue (83%), hypertension (75%), and hand-foot syndrome (65%). The most common grade 3 adverse events were hypertension (60%) dehydration (10%), hand-foot syndrome (8%), and fatigue (8%); one grade 4 event (elevated lipase) was observed. Serious adverse events considered likely related to therapy occurred in 20% of patients, with the most common being dehydration (10%) and diarrhea (5%). No treatment-related deaths were reported.
The investigators concluded: “Individualized axitinib dosing in patients with metastatic renal cell carcinoma 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. These prospective results warrant consideration of axitinib in this setting.”
Moshe C. Ornstein, MD, of the Cleveland Clinic’s Taussig Cancer Center, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Pfizer. For full disclosures of the study authors, visit thelancet.com.
