Sunitinib prolongs progression-free and overall survival, and is safe and well tolerated in advanced kidney cancer (metastatic renal cell carcinoma) patients with a poor prognosis such as the elderly and those whose cancer has spread to the brain, finds an article in The Lancet Oncology.

Sunitinib is an oral targeted drug that attacks cancer by inhibiting tumour growth and starving the tumour of blood, reducing its ability to divide and grow. In previous trials sunitinib has shown clear benefit in patients with advanced kidney cancer and has been approved worldwide for first and second-line treatment in these patients. However, certain patients with advanced kidney cancer—often those with a poor prognosis such as those whose cancer has spread to the brain, those with a poor performance status (PS), and the elderly—are often excluded or inadequately represented in clinical trials. Thus, little is known about the activity, safety, and tolerability of sunitinib in these patients.

To resolve this uncertainty, Martin Gore and colleagues conducted an international expanded-access trial including subgroups of patients with advanced kidney cancer not usually entered into clinical trials, or those being treated in countries where the drug is not yet approved who would not normally receive the drug.

In total, 4,564 patients from 52 countries were recruited between June 2005 and December 2007. These included four subgroups of patients with brain metastases (321), poor performance status (582), non-clear-cell renal cell carcinoma (588), and patients aged 65 years or older (1,418). Patients received 50mg of sunitinib once daily in repeated 6-week cycles of 4 weeks of treatment followed by 2 weeks off. Tumour response, toxicity, and adverse events were assessed at regular intervals.

Overall, findings showed that sunitinib can be given safely and is well tolerated in all four subgroups of patients that might be expected to have a lower tolerance to therapy than the broader advanced kidney cancer patient population. Indeed, the safety profile was found to be very similar to that reported in previous trials and the overall incidence of adverse events was slightly less.

The most common treatment-related adverse events (AEs) were diarrhoea (44%) and fatigue (37%). Importantly, there were no differences in incidences of grade 3 and 4 AEs between the overall population and patients with brain metastases, poor PS, non-clear RCC, and the elderly—with fatigue (8%) and thrombocytopenia (8%) reported as the most common.

Median progression-free and overall survival were 10.9 and 18.4 months respectively, an improvement on historical data. The overall objective response rate (ORR) was 17%, with all four subgroups showing clear evidence of response—brain metastases (12%), non-clear RCC (11%), poor PS (9%), and the elderly (17%).

The authors say that these results should: “Encourage the study of targeted agents in subgroups of patients otherwise excluded from trials and therefore potentially disadvantaged.”

In an accompanying Reflection and Reaction comment, Dr Joaquim Bellmunt, Hospital del Mar, Barcelona, Spain and and Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA, and Dr Toni K Choueiri, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA, say: “As with sorafenib, the safety and efficacy of sunitinib in an older population are confirmed and evidence shows that age alone should not be a deterrent from attempting therapy. However, patients with brain metastases, non-clear-cell histology, and poor performance status benefit less from sunitinib, despite good drug tolerance, suggesting the need for prospective studies in these subpopulations. Thus, claiming sunitinib as a ‘standard’ in these subgroups remains controversial. 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.”