Efficacy and safety of first-line sunitinib in Chinese patients with metastatic renal cell carcinoma.

AIM: We report the first prospective study of sunitinib for metastatic renal cell carcinoma (mRCC) in China. METHODS: Chinese mRCC patients received first-line sunitinib 50 mg daily (4/2 regimen). Overall survival (OS), progression-free survival (PFS), objective response rate and safety were assessed. Potential efficacy biomarkers were explored in post hoc analyses. RESULTS: Median PFS was 61.7 weeks; median OS was 133.4 weeks; objective response rate was 31.1%. Most frequent adverse events (AEs) were: hand-foot syndrome (63.8%), decreased white blood cell count (52.4%), fatigue (51.4%) and decreased platelet count (51.4%). AEs were identified that predicted longer PFS and OS. CONCLUSION: Sunitinib showed efficacy and manageable AE profile in treatment-naive Chinese mRCC patients. Larger prospective studies are required to confirm identified AEs as predictors of efficacy.

Safety and efficacy of sunitinib in patients from Latin America: subanalysis of an expanded access trial in metastatic renal cell carcinoma.

BACKGROUND: Sunitinib is an approved treatment for metastatic renal cell carcinoma (mRCC). The safety profile and efficacy of sunitinib were confirmed in a global expanded access trial (ClinicalTrials.gov identifier: NCT00130897). This report presents a subanalysis of the final trial data from patients in Latin America. METHODS: Treatment-naïve or previously treated mRCC patients aged ≥18 years received oral sunitinib at a starting dose of 50 mg/day on a 4-weeks-on/2-weeks-off schedule. Treatment continued until disease progression, unacceptable toxicity, or withdrawal of consent. Safety was assessed regularly, and tumor measurements were scheduled per local practice (using Response Evaluation Criteria in Solid Tumors). RESULTS: In total, 348 patients from Latin America received sunitinib. Overall, 75% of patients had two or more sites of metastatic disease, 28% were aged ≥65 years, 14% had an Eastern Cooperative Oncology Group performance status ≥2, 9% had brain metastases, 9% had no prior nephrectomy, and 5% had non-clear cell RCC. Median treatment duration was 8 months, and median follow-up was 15.1 months. In total, 326 patients (94%) discontinued treatment, primarily due to death (41%) or lack of efficacy (22%). Most treatment-related adverse events were of mild to moderate severity (grade 1/2). Mucosal inflammation (reported in 54% of patients), diarrhea (53%), and asthenia (41%) were the most common any-grade treatment-related adverse events. Asthenia (12%), neutropenia (10%), and fatigue and thrombocytopenia (both 9%) were the most common grade 3/4 treatment-related adverse events. In total, 311 patients were included for tumor response, of whom eight (3%) had a complete response and 46 (15%) a partial response, yielding an objective response rate of 17%. Median duration of response, progression-free survival, and overall survival were 26.7, 12.1, and 16.9 months, respectively. CONCLUSION: The efficacy and safety profile of sunitinib in patients with mRCC from Latin America was comparable to that in the entire cohort of the global expanded access trial.

Bisphosphonates in patients with renal cell carcinoma and bone metastases: a sunitinib global expanded-access trial subanalysis.

AIM: To investigate retrospectively the effects of bone metastases and bisphosphonates in sunitinib-treated metastatic renal cell carcinoma patients. PATIENTS & METHODS: Patients in Groups (Gp) 1 and 2, but not Gp3, had bone metastases. Gp2 received bisphosphonates following standard practice. RESULTS: Gp2 had less favorable prognosis than Gp1. Gp3 had fewer metastases and the best prognosis. More serious adverse events occurred in Gp2 versus Gp1. The difference in overall survival between Gp1 and Gp2 was not significant after adjusting for covariates. Significantly shorter overall survival in Gp1 versus Gp3 persisted after adjusting for covariates. CONCLUSION: Bone metastases may have a negative prognostic impact in metastatic renal cell carcinoma. Bisphosphonates may have delayed early disease progression for prognostically worse sunitinib/bisphosphonate-treated patients.

Central and Eastern European experience with sunitinib in metastatic renal cell carcinoma: a sub-analysis of the global expanded-access trial.

A global, open-label, expanded-access trial (EAT) provided sunitinib treatment on a compassionate-use basis to patients with metastatic renal cell carcinoma (mRCC) between 2005 and 2011. This retrospective analysis examines outcomes in patients from Central and East European (CEE) countries participating in the global EAT. Sunitinib (starting dose 50 mg orally once daily, with dose reduction for toxicity) was administered in repeated 6-week cycles (4 weeks on and 2 weeks off) until occurrence of disease progression or unacceptable toxicity. Tumor assessments were guided by Response Evaluation Criteria in Solid Tumors (RECIST) criteria but were performed according to local standards of care. In total, 401 CEE patients received sunitinib (median treatment duration 9.6 months), of whom 378 were evaluable for tumor response. The most frequent grade ≥3 toxicities were fatigue (7.5 %), hypertension (7.0 %), thrombocytopenia (6.5 %), diarrhea (4.2 %), nausea and hand-foot syndrome (both 3.7 %) and neutropenia (3.0 %). Median overall survival was 30.7 months (95 % CI 23.3, ‒ months). Overall survival tended to be longer in cytokine-naïve than cytokine-experienced patients (median 60.8 vs. 27.5 months; P = 0.1324). Among patients with evaluable tumors, 4.0 % achieved a complete and 14.6 % a partial response [objective response rate (ORR) 18.5 % (95 % CI 14.7, 22.8 %)]. Median progression-free survival was 11.6 months (95 % CI 10.3, 12.8 months). Sunitinib demonstrates safety and effectiveness in real-world mRCC patients in CEE countries. Expanded-access program patients showed a lower tumor response rate but similar survival outcomes to patients in the pivotal Phase III clinical trial of sunitinib in mRCC.