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Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial
Martin E Gore1, Cezary Szczylik, Camillo Porta
1Royal Marsden Hospital NHS Trust, London, UK. martin.gore@rmh.nhs.uk
Background:
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.
Methods:
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.
Findings:
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).
Interpretation:
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.
Funding:
Pfizer Inc.
Insights
Sunitinib demonstrated a manageable safety profile and encouraging efficacy in a broad population of patients with metastatic renal-cell carcinoma (RCC). These results are particularly notable in subgroups with poor prognosis, who often do not meet clinical trial criteria.
Area of Science:
- Oncology
- Pharmacology
Background:
- Sunitinib is a standard first-line treatment for advanced or metastatic renal-cell carcinoma (RCC).
- Limited data exist on sunitinib's efficacy in patient subgroups not meeting clinical trial inclusion criteria, especially those with poorer prognoses.
- This study aimed to provide sunitinib compassionately to trial-ineligible RCC patients in countries without regulatory approval.
Purpose of the Study:
- To evaluate the safety and efficacy of sunitinib in a broad, real-world population of patients with metastatic RCC.
- To assess sunitinib's activity in patient subgroups typically excluded from clinical trials, such as those with brain metastases, poor performance status, non-clear-cell histology, or advanced age.
Main Methods:
- Open-label, compassionate-use study of sunitinib 50 mg orally once daily (4 weeks on, 2 weeks off).
- Included previously treated and treatment-naive adult patients with metastatic RCC.
- Safety assessed regularly; tumor measurements and survival data collected. Analysis in the modified intention-to-treat (ITT) population.
Main Results:
- 4564 patients enrolled; 4371 in the modified ITT population, including subgroups with brain metastases (7%), ECOG performance status ≥2 (13%), non-clear-cell RCC (13%), and age ≥65 years (32%).
- Objective response rate (ORR) was 17% overall. Subgroup ORRs ranged from 9% (ECOG ≥2) to 17% (age ≥65).
- Median progression-free survival was 10.9 months; median overall survival was 18.4 months. Common adverse events included diarrhea and fatigue; Grade 3-4 events were similar across subgroups.
Conclusions:
- Sunitinib 50 mg daily on a 4/2 schedule has a manageable safety profile in a broad metastatic RCC population.
- Efficacy results are encouraging, especially in subgroups with poor prognostic factors typically excluded from clinical trials.
- This study supports the use of sunitinib in a wider range of metastatic RCC patients.
