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

Abstract

BackgroundSunitinib 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.MethodsTreatment-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).ResultsIn 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.ConclusionThe 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.

Sex-Divergent Clinical Outcomes and Precision Medicine: An Important New Role for Institutional Review Boards and Research Ethics Committees

“…Last, sex-divergent differences in clearance and volume of distribution parameters between male and female patients have been shown ( Khosravan et al, 2016 ) which suggests clinical translatability from preclinical studies. The pharmacokinetic differences between male and female sexes may be responsible for the large variability and lack of efficacy encountered in some clinical trials which led to the change or discontinuation of treatment ( Lankheet et al, 2014b ; Akaza et al, 2015 ; Gore et al, 2015 ; Barrios et al, 2016 ; Domagała-Haduch et al, 2016 ) likely due to poor dosing adjustment since plasma concentration alone may not ensure precise dose adjustment ( Houk et al, 2010 ; Lankheet et al, 2014b ) as seen in most TK inhibitors ( de Wit et al, 2015 ; Kotecki and Penel, 2016 ). This is especially relevant if sex differences lead to tissue exposure differences as observed in the preclinical studies, are not taken into account.…”

The effect of apatinib in the treatment of metastatic renal cell carcinoma: a case report and review of the literature

“…In a study in a Latin-American population, sunitinib has been confirmed to be safe and effective even with worse prognosis. The median PFS (mPFS) and OS were 12.1 and 16.9 months, respectively, while neutropenia, thrombocytopenia and anemia were common adverse hematologic events 7. Rovithi et al8 indicated that the optimal treatment with sunitinib was based on a pulsatile, high-dose strategy, which led to an antitumor effect.…”

“…Clinically, apatinib, an oral antiangiogenic agent, is widely used during the treatment of different tumors. In particular, apatinib is the most common targeted agent aiming to improve progression-free survival (PFS) and overall survival (OS) of patients with advanced gastric cancer (AGC) and metastatic gastric cancer (mGC) after failure of chemotherapy 7. Nevertheless, few publications related to the effect and safety of apatinib in treating mRCC have been found.…”

Longitudinal Pharmacometabonomics for Predicting Malignant Tumor Patient Responses to Anlotinib Therapy: Phenotype, Efficacy, and Toxicity

“…The most common grade 3 AEs related to anlotinib were proteinuria, hypertension, fatigue, dyslipidemia, and hand-foot skin reactions (2,8,9). Though, it was revealed that anlotinib administration showed less and milder diarrhea than other oral anti-VEGFR receptor tyrosine kinase inhibitors (10)(11)(12). It should pay attention that patients undergoing anlotinib treatment still had a high occurrence of AEs.…”