Prior Sunitinib Duration Affects Second-Line RCC Therapy Outcomes

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SAN FRANCISCO—Prior sunitinib treatment for nine months or longer may be associated with a longer progression-free survival (PFS) in patients with metastatic renal cell carcinoma (RCC) receiving axitinib as second-line treatment, according to a new study presented at the 2012 Genitourinary Cancer Symposium.

Brian Rini, MD, Associate Professor of Medicine at Cleveland Clinic, and his colleagues evaluated the effect of prior sunitinib treatment duration and axitinib dose titration on subsequent axitinib efficacy. Axitinib is a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3.

The FDA recently approved axitinib (Inlyta) to treat patients with advanced RCC who have not responded to another RCC drug. In the phase 2 AXIS trial of axitinib versus sorafenib for second-line mRCC, axitinib significantly prolonged median PFS (6.7 vs 4.7 months).

In the current trial, eligible patients had clear-cell mRCC with measurable RECIST-defined progressive disease after one prior first-line systemic therapy. Investigators randomized patients to either axitinib at a starting dose of 5 mg twice daily or sorafenib 400 mg twice a day.

Among other factors, investigators wanted to look at dosing and analyze which patients could tolerate doses of 10 mg a day. Patients without toxicities greater than grade 2 and blood pressure less than 150/90 mm Hg and who were without antihypertensive medication for more than two weeks were eligible to have their axitinib dose increased to 7 mg twice a day and then to 10 mg twice a day.

The median PFS was 6.6 months for 132 patients receiving at least one total daily axitinib dose greater than 10 mg (dose-titrated group) and 8.3 months for 227 patients receiving an axitinib dose of 10 mg or less. A total of 194 patients (53.7%) in the axitinib arm and 195 (53.9%) in the sorafenib arm had prior sunitinib treatment.

The median PFS for duration of prior sunitinib treatment for nine months or more and less than nine months was 6.3 months and 4.5 months, respectively, for axitinib patients. The median PFS for duration of prior sunitinib treatment of nine months or more and less than nine months was 4.6 months and 2.9 months, respectively, for sorafenib patients.

The investigators concluded that duration of prior sunitinib treatment for nine months or more may be associated with a longer PFS on second-line VEGFR tyrosine kinase inhibitors. The study also showed that both axitinib dose-increased and non-increased patients had longer PFS compared with the sorafenib arm.

“If people are at sub-therapeutic levels they are very unlikely to respond to it,” Dr. Rini told Renal & Urology News. “We need to optimize drug levels. Dose titration allows people to meet the minimum requirements.”

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