MIAMI—Dose-escalation of tyrosine kinase inhibitors (TKIs) after disease progression in select patients with metastatic renal cell carcinoma (mRCC) can reduce tumor burden and prolong the duration of therapy, a study presented at the 14th International Kidney Cancer Symposium (IKCS) has shown.1

Because TKIs have a high variability in drug levels in patients with mRCC, researchers sought to evaluate whether dose-escalation at the time of disease progression may impact tumor burden.

For the study, researchers identified and analyzed data from 22 patients with mRCC who were treated at Cleveland Clinic in Ohio with TKIs and were dose-escalated following disease progression per RECIST 1.1 criteria. Of those, 82% were male, 77% had clear cell histology, 95% had prior nephrectomy, and 77% were intermediate risk per International mRCC Database Consortium (IMDC) criteria.

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Results showed that axitinib was the most common dose-escalated TKI in patients, followed by sunitinib and pazopanib.

Researchers found among the 17 patients with evaluable tumor measurements after TKI dose-escalation, 82% had a reduction in tumor burden with a median decrease of 14%.

“Twenty-four percent of patients experienced a tumor burden decrease of more than 30%,” said Moshe C. Ornstein, MD, MA, of the Cleveland Clinic Taussig Cancer Institute in Cleveland, OH.

Prior to disease progression and dose-escalation, the median treatment duration was 6.8 months. The median treatment duration of escalated therapy was estimated by investigators to be 6.7 months.

“At the time of this analysis, 7 patients continue to be treated at escalated TKI doses,” concluded Dr. Ornstein.


  1. Ornstein MC, Wood L, Elson P, et al. Clinical Effect of TKI Dose-Escalation after Disease Progression in Patients with Metastatic Renal Cell Carcinoma [abstract]. BJU Int. 2015. doi: 10.1111/bju.13365.