Patients with advanced kidney cancer—traditionally one of the most difficult-to-treat of all cancer types—are being given new hope in the form of drugs that inhibit tumor angiogenesis, or new blood vessel growth. Two antiangiogenic agents, sunitinib (Sutent®) and sorafenib (Nexavar®), have been FDA approved to treat advanced forms of the disease, including kidney cancer that has spread to other organs. These therapies, which are administered as pills, interfere with the chemical signaling between tumors and blood vessels, thereby blocking angiogenesis and essentially starving the tumor of oxygen and nutrients. A landmark clinical study published in 2007 showed that sunitinib dramatically prolongs the amount of time a patient lives without his/her disease getting worse, a benefit known as improved progression-free survival (PFS)1.

While these findings established sunitinib as a new standard of care for advanced kidney cancer, many patients considered by oncologists to have a “poor prognosis”, such as the elderly and those with brain metastasis or other disease features that often negatively impact treatment outcome, were excluded from the original clinical trial. Now, results from a multinational, expanded access study shows that sunitinib prolongs overall survival (OS) as well as PFS, and is safe and well tolerated in many advanced kidney cancer patients with a poor prognosis2. The new findings will be published in the August issue of the international medical journal Lancet Oncology.

In this study, 4,564 patients from 52 countries were enrolled between June 2005 and December 2007. These included 4 subgroups of patients with poorer prognosis: 1) those with brain metastases; 2) poor performance status; 3) non-clear-cell renal cell carcinoma; and 4) age of 65 years or older. Patients were given sunitinib at the standard, approved dosing of 50 mg once daily in repeated 6-week cycles, with 4 weeks on treatment followed by 2 weeks off treatment. During the study, the researchers examined tumor shrinkage, as well as side effects caused by treatment.

Overall, sunitinib was generally well tolerated in all 4 subgroups of patients that might be expected to have a lower therapy tolerance than other patients with kidney cancer due to the extent of their disease, advanced age, or other underlying health problems. The severity of side effects was found to be similar to those reported in previous trials of sunitinib, and the overall incidence of side effects was slightly lower. The most common treatment-related side effects were diarrhea (44%) and fatigue (37%). Notably, “poor prognosis” patients had no greater frequency of severe side effects than has been observed in other studies of sunitinib for advanced kidney cancer. In the current trial, physicians were allowed to reduce their patients’ sunitinib dose from the standard 50 mg/day (4 weeks on, 2 weeks off) to 37.5 mg/day taken continuously, in order to help alleviate side effects. One third of the patients had their sunitinib dose reduced, which may explain the relatively low occurrence of side effects in this trial.

The median PFS was 10.9 months and OS was 18.4 months, an improvement over historical results using standard advanced kidney cancer therapies. In addition, 17% of patients had a decrease in tumor size (objective response), and all 4 patient subgroups showed clear evidence of response: brain metastases (12%), non-clear cell RCC (11%), poor PS (9%), and the elderly (17%). It should be noted, however, that response data was not collected from 21% of the patient population.

Commenting on the study, Dr. Joaquim Bellmunt, of the Hospital del Mar, Barcelona, Spain and Dana-Farber Cancer Institute, and Dr. Toni K Choueiri, from Dana-Farber Cancer Institute, say that the study results indicate that advanced age alone should not deter physicians from sunitinib therapy for advanced kidney cancer. They add that the use of sunitinib in the other 3 subgroups remains unproven, but that based on available information the use of sunitinib may be justified in these populations if access to clinical trials is not available.