Sunitinib for Asian Patients with Advanced Renal Cell Carcinoma: A Comparable Efficacy with Different Toxicity Profiles

Abstract

Objective: We aimed to describe the efficacy and safety of sunitinib in unselected Korean advanced renal cell carcinoma (RCC) patients. Patients and Methods: From November 2005 to August 2008, 132 histologically confirmed advanced RCC patients (100 in the global expanded access program) were enrolled. Response and toxicity were assessed regularly according to the protocol. Results: Within this population, 82.6% had clear cell RCC, and 28.8% were treatment naïve. Patients received a median of 5 cycles of sunitinib (range 1–30), and the mean relative dose intensity was 82.0 ± 14.20 (SD). The progression-free survival (PFS) and overall survival rates were 8.2 and 23.1 months, respectively. For the 130 evaluable patients, the objective response rate was 34.1% (n = 45); 44.7% (n = 59) exhibited stable disease. Reasons for discontinuation were disease progression (75.0%) and toxicity (7.6%). The most frequent adverse events were thrombocytopenia (75.0%), neutropenia (70.5%), and anemia (69.7%). Low body surface area (OR = 4.2, 95% CI 1.2–13.8, p = 0.02) and previously treated status (OR = 3.1, 95% CI 1.3–7.4, p = 0.01) were highly predictive of grade 3–4 toxicities. Based on these findings, a nomogram predicting the probability of 12-month PFS was constructed, giving a concordance index of 0.675. Conclusions: Despite the different toxicity profiles, maintaining adequate dose modifications and a careful follow-up enables comparable treatment outcomes for unselected Korean advanced RCC patients.

Efficacy and safety of vascular endothelial growth factor receptor tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma and poor risk features

“…We found that grade 3 or worse neutropenia, thrombocytopenia, and hand-foot syndrome due to sunitinib are more common in our study (21, 17, and 12%, respectively) than in pivotal phase III trials (12, 8, and 5%, respectively) ). These higher toxicity proWles are consistent with previous studies of sunitinib in ethnically Asian patients with mRCC (Yoo et al 2010;Kim et al 2011;Tomita et al 2010), which reported that similar eYcacy and higher incidences of severe neutropenia, thrombocytopenia, and hand-foot syndrome compared with Caucasian. The current study results suggested that these trends are also applicable to poor-risk patients.…”

“…The most frequent grade 2-3 non-hematologic toxicities were hand-foot syndrome (27%), hypertension (24%), fatigue (23%), and stomatitis (23%). The incidence of adverse events to sunitinib was in agreement with previous reports in Asian patients (Yoo et al 2010;Kim et al 2011;Tomita et al 2010).…”

Chemotherapy in metastatic renal cell carcinoma today? A systematic review

“…A further research scenario may be represented by the combination of targeted agents with chemotherapy for Choueiri et al [128] Sunitinib and sorafenib efficacy in PRCC and ChRCC Any 53 12 (23) Gore et al [129] Sunitinib safety and efficacy Any 4371 NR Stadler et al [130] Sorafenib North America ARCCS Any 2504 NR Kim et al [131] Sunitinib efficacy and toxicity in Asian patients Any 132 a 52 (39) Beck et al [132] Sorafenib Europe EU-ARCCS Any 1150 NR Grü nwald et al [133] Everolimus safety and efficacy after VEGFr-TKI Any 1367 195 (14) those patients with mixed histology (sarcomatoid and clear cell components), whereas a theoretical additive (or synergic) activity may be suggested [99,100].…”

Regorafenib for advanced gastrointestinal stromal tumors following imatinib and sunitinib treatment: a subgroup analysis evaluating Japanese patients in the phase III GRID trial

“…In studies assessing sunitinib in patients with advanced renal-cell carcinoma (RCC), Korean and Japanese investigators independently reported that patients in their countries showed clinical efficacy that was at least as good as that seen in global studies, while incidences of hematologic AEs were higher than those observed in Western patients [13,14]. Similarly, analysis of a study comparing axitinib and sorafenib in patients with metastatic RCC showed a higher incidence of some AEs in Japanese patients than in the overall study population [15].…”