Axitinib active in treatment-naive metastatic renal cell carcinoma

First-line therapy with axitinib demonstrated clinical activity in metastatic renal cell carcinoma, and dose titration with axitinib is associated with a higher rate of objective response than placebo titration, according to results of a randomized phase 2 study.

In the double blind, multicenter study, Brian I. Rini, MD, of the department of solid tumor oncology at Cleveland Clinic’s Taussig Cancer Institute, and colleagues compared the safety and efficacy of axitinib (Inlyta, Pfizer) dose titration vs. placebo titration in patients with previously untreated metastatic renal-cell carcinoma.

Brian I. Rini

Rini, a HemOnc Today Editorial Board member, and colleagues enrolled 213 patients at 49 hospitals and outpatient clinics in the United States, Czech Republic, Germany, Japan, Russia and Spain.

All patients received 5 mg twice-daily axitinib — a small-molecule tyrosine kinase inhibitor — during a 4-week lead-in period.

After the lead-in period, the 112 patients with blood pressure of 150/90 mm Hg or lower who experienced no grade 3 or grade 4 treatment-related toxicities, required no dose reductions during the lead-in period, and used no more than two antihypertensive drug for 2 consecutive weeks were deemed eligible for dose titration with either axitinib or placebo.

Rini and colleagues stratified the 112 eligible patients by ECOG performance status (0 vs. 1). Researchers randomly assigned 56 patients to masked titration with axitinib (twice daily doses of 7 mg, then 10 mg if tolerated). The other 56 patients were assigned to placebo titration.

Objective response served as the primary outcome. Safety assessment was based on all patients who received at least one dose of axitinib.

Researchers reported a higher objective response rate in the axitinib titration group (54% vs. 34%; P=.019).

Rates of grade ≥3 hypertension (18% vs. 9%), diarrhea (13% vs. 4%) and decreased weight (7%vs. 5%) were higher in the axitinib titration group.

“The greater proportion of patients in the axitinib titration group achieving an objective response supports the concept of individual axitinib dose titration in selected patients with metastatic renal-cell carcinoma,” Rini and colleagues wrote. “Axitinib shows clinical activity with a manageable safety profile in treatment-naive patients with this disease.”

In an accompanying editorial, Sebastiano Buti, MD, of the medical oncology unit at University Hospital in Parma, Italy, and Camillo Porta, MD, of IRCCS San Matteo University Hospital Foundation in Pavia, Italy, wrote: “Perhaps we should revise our way of thinking about how we administer tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma; perhaps these drugs have more in common with chemotherapy than we thought. Nevertheless, dose titration to toxicity is not yet ready to become standard practice, given that it does not seem easily applicable to the majority of patients, due to the greater toxicity and subsequent possible resistance by patients and physicians themselves.”

For more information:

Buti S. Lancet Oncol. 2013;doi: 10.1016/S1470-2045(13)70489-3.
Rini BI. Lancet Oncol. 2013;doi:10.1016/S1470-2045(13)70464-9.

Disclosure: The researchers report research funding, honoraria and lecture fees from, advisory and speakers’ bureau roles with, stock ownership in and employment relationships with Pfizer. They also report financial relationships with several other pharmaceutical companies.