Pazopanib Outscores Sunitinib on Tolerability

The tyrosine kinase inhibitor (TKI) pazopanib (Votrient; GlaxoSmithKline) scored higher on quality-of-life indices than the more widely used TKI sunitinib (Sutent; Pfizer) in treating metastatic renal cell carcinoma (RCC), in a study reported in the New England Journal of Medicine.

The drugs offer comparable progression-free survival (PFS), making pazopanib the better alternative, says the study's senior author, Toni Choueiri, MD, director of the kidney cancer center at Dana-Farber Cancer Institute and Brigham and Women's Hospital in Boston, MA. “The efficacy is the same, but pazopanib is better tolerated, so that's probably the more appropriate drug to start with,” he says.

Choueiri and colleagues launched their investigation in response to indirect evidence that pazopanib and sunitinib offer similar PFS benefits of roughly 11 months each. That evidence came from earlier studies in untreated patients with metastatic RCC: one trial compared pazopanib with placebo and another compared sunitinib with interferon α. However, the drugs had never been compared head to head, so the researchers initiated a noninferiority study to confirm that one isn't appreciably worse than the other in terms of safety and tolerability.

During the phase III randomized trial, 1,100 patients were assigned to receive pazopanib given daily or sunitinib given in 6-week cycles—once daily for 4 weeks, followed by 2 weeks without treatment. At 8.4 months, the median PFS for pazopanib was not significantly different from the 9.5 months achieved with sunitinib.

However, pazopanib scored consistently higher on 11 of 14 quality-of-life measures, including fatigue and mouth sores that, Choueiri says, can interfere with patients' ability to obtain adequate nutrition. Moreover, pazopanib scored better on measures of medical resource use, such as unscheduled office visits, phone consultations, and trips to the emergency room.

Nizar Tannir, MD, the deputy chair in genitourinary medical oncology at The University of Texas MD Anderson Cancer Center in Houston, says the results back up anecdotal observations that patients find pazopanib “easier to take” than sunitinib.

One possible caveat of the study, he points out, is that patients filled out quality-of-life assessments at 28-day intervals, when toxicity from sunitinib's 4-week treatment cycle is peaking. “Responses could have been different if the questionnaires were filled out at the first day of a new treatment cycle,” he says.

Clinicians at MD Anderson shifted first-line treatment protocols for metastatic RCC to pazopanib in 2010, because their experience suggested that the drug was more tolerable than sunitinib and induced less bone marrow suppression, says Tannir.

Joanna Brell, MD, head of cancer toxicity and symptom research at the National Cancer Institute, cautions that pazopanib induces more liver toxicity than sunitinib. “If a patient's liver function tests don't look good, then pazopanib might not be the right drug to take,” she says. “However, it does look like sunitinib is the more toxic drug overall.”