Sunitinib prolongs survival in advanced, kidney cancer

NEW YORK (Reuters Health) - The antineoplastic agent sunitinib, an inhibitor of multiple receptor tyrosine kinases, prolongs survival in patients with metastatic renal cell carcinoma, even in patients normally excluded from clinical trials because of their poor prognosis.

Sunitinib is considered a standard of care for first-line treatment of advanced or metastatic renal cell carcinoma. However, patients predicted to not tolerate therapy very well - such as those with brain metastases, a poor performance status, non-clear-cell histology, or older age -- have generally been excluded from the clinical trials that established its benefit for advanced renal cell carcinoma.

"The primary objective of this trial was to provide sunitinib on a compassionate-use basis to trial-ineligible patients with renal cell carcinoma from countries where regulatory approval had not been granted," lead author Dr. Martin Gore and colleagues state in the August issue of The Lancet Oncology. Enrollment took place between 2005 and 2007.

More than half of the patients were affected by at least one of the mentioned contraindications (brain metastases, n = 321; Eastern Cooperative Oncology Group performance status of 2 or higher, n = 582; non-clear-cell histology, n = 588; and age 65 and older, n = 1414).

Patients in the modified intent-to-treat population (n = 4371) were treated with sunitinib at a starting dose of 50 mg daily in repeated cycles of 4 weeks on treatment followed by 2 weeks off. Dose reductions were permitted as needed.

"The progression-free survival and overall survival data are very consistent with previous reports and show improvement on historical data for the subgroups reported here," the authors note.

Median overall survival was 18.4 months, comparable to rates in previous trials, as was that for elderly patients (18.2 months). Progression-free survival was 10.9 months overall, and 11.3 months for elderly patients. In the other groups, median progression-free survival ranged from 5.1 to 7.8 months.

"We have shown that sunitinib is safe and toxicity manageable in subgroups of patients that might otherwise have lower tolerance to therapy," Dr. Gore's group maintains. "Efficacy appears to be consistent with the benefits shown in prospective renal cell carcinoma studies."

In a linked commentary, Dr. Toni K. Choueiri from the Harvard Medical School, Boston, and Dr. Joaquim Bellmunt from Universitat Pompeu Fabra, Barcelona, point out that "patients with brain metastases, non-clear-cell histology, and poor performance status benefit less from sunitinib."

This suggests the "need for prospective studies in these subpopulations."

"An oncologist might not have access to such trials in practice, however, and based on available information the use of sunitinib may be justified in these subpopulations."

The trial was sponsored and designed by Pfizer in collaboration with the investigators.

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