Results from clinical trials have established sunitinib as a standard of care for
first-line treatment of advanced or metastatic renal-cell carcinoma (RCC); however,
many patients, particularly those with a poorer prognosis, do not meet inclusion criteria
and little is known about the activity of sunitinib in these subgroups. The primary
objective of this trial was to provide sunitinib on a compassionate-use basis to trial-ineligible
patients with RCC from countries where regulatory approval had not been granted.
Previously treated and treatment-naive patients at least 18 years of age with metastatic
RCC were eligible. All patients received open-label sunitinib 50 mg orally once daily
on schedule 4-2 (4 weeks on treatment, 2 weeks off). Safety was assessed regularly,
tumour measurements done per local practice, and survival data collected where possible.
Analyses were done in the modified intention-to-treat (ITT) population, which consisted
of all patients who received at least one dose of sunitinib. This study is registered
with ClinicalTrials.gov, NCT00130897.
As of December, 2007, 4564 patients were enrolled in 52 countries. 4371 patients were
included in the modified ITT population. This population included 321 (7%) patients
with brain metastases, 582 (13%) with Eastern Cooperative Oncology Group (ECOG) performance
status of 2 or higher, 588 (13%) non-clear-cell RCC, and 1418 (32%) aged 65 years
or more. Patients received a median of five treatment cycles (range 1-25). Reasons
for discontinuation included lack of efficacy (n=1168 [27%]) and adverse events (n=362
[8%]). The most common treatment-related adverse events were diarrhoea (n=1936 [44%])
and fatigue (n=1606 [37%]). The most common grade 3-4 adverse events were fatigue
(n=344 [8%]) and thrombocytopenia (n=338 [8%]) with incidences of grade 3-4 adverse
events similar across subgroups. In 3464 evaluable patients, the objective response
rate (ORR) was 17% (n=603), with subgroup ORR as follows: brain metastases (26 of
213 [12%]), ECOG performance status 2 or higher (29 of 319 [9%]), non-clear-cell RCC
(48 of 437 [11%]) and age 65 years or more (176 of 1056 [17%]). Median progression-free
survival was 10.9 months (95% CI 10.3-11.2) and overall survival was 18.4 months (17.4-19.2).
In a broad population of patients with metastatic RCC, the safety profile of sunitinib
50 mg once-daily (initial dose) on schedule 4-2 was manageable and efficacy results
were encouraging, particularly in subgroups associated with poor prognosis who are
not usually entered into clinical trials.
Pfizer Inc.