Toxicity-Based Titration of Axitinib in Metastatic Kidney Cancer
Posted: Thursday, October 24, 2019
Individualized drug regimens, following treatment with checkpoint inhibitor therapy, may improve clinical outcomes for patients with metastatic renal cell carcinoma. The findings of a prospective phase II single-arm study investigating toxicity-based dosing of the VEGFR tyrosine kinase inhibitor axitinib were published in The Lancet Oncology.
“This trial did not show a relationship between drug dose and response, highlighting that different patients achieve different drug exposures with the same drug dose and that titration on the basis of toxicity best achieves the optimal axitinib exposure for clinical outcome in each patient,” revealed Mosche C. Ornstein, MD, of the Taussig Cancer Institute, Cleveland.
The trial enrolled 40 patients who were initially treated with 5 mg of axitinib twice daily. If unaccompanied by axitinib-related grade 2 adverse events, the dose was increased in 1-mg increments every 14 days, with a maximum dose of 10 mg. The median follow up was 8.7 months. Although the study did not achieve the primary outcome of median progression-free survival of 9.5 months or more at 8.8 months, 45% achieved an objective response, with a prolonged response lasting more than 12 months in 67% of those patients.
The most common grade 3 adverse events were fatigue (8%), hand-foot syndrome (8%), and hypertension (60%). One patient experienced a grade 4 adverse event of elevated lipase levels. Serious adverse events occurred in 20% of patients, with dehydration and diarrhea being the most common. No patient discontinued treatment due to adverse events, and there were no recorded axitinib-related deaths.
Disclosure: The study authors’ disclosure information can be found at thelancet.com.