Safety and efficacy of everolimus in Chinese patients with metastatic renal cell carcinoma resistant to vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy: an open-label phase 1b study

Abstract

BackgroundIn China, there are currently no approved therapies for the treatment of metastatic renal cell carcinoma (mRCC) following progression with vascular endothelial growth factor (VEGF)-targeted agents. In the phase 3 RECORD-1 trial, the mammalian target of rapamycin (mTOR) inhibitor everolimus afforded clinical benefit with good tolerability in Western patients with mRCC whose disease had progressed despite VEGF receptor-tyrosine kinase inhibitor (VEGFr-TKI) therapy. This phase 1b study was designed to further evaluate the safety and efficacy of everolimus in VEGFr-TKI-refractory Chinese patients with mRCC.MethodsAn open-label, multicenter phase 1b study enrolled Chinese patients with mRCC who were intolerant to, or progressed on, previous VEGFr-TKI therapy (N = 64). Patients received everolimus 10 mg daily until objective tumor progression (according to RECIST, version 1.0), unacceptable toxicity, death, or study discontinuation for any other reason. The final data analysis cut-off date was November 30, 2011.ResultsA total of 64 patients were included in the study. Median age was 52 years (range, 19–75 years) and 69% of patients were male. Median duration of everolimus therapy was 4.1 months (range, 0.0-16.1 months). Expected known class-effect toxicities related to mTOR inhibitor therapy were observed, including anemia (64%), hypertriglyceridemia (55%), mouth ulceration (53%), hyperglycemia (52%), hypercholesterolemia (50%), and pulmonary events (31%). Common grade 3/4 adverse events were anemia (20%), hyperglycemia (13%), increased gamma-glutamyltransferase (11%), hyponatremia (8%), dyspnea (8%), hypertriglyceridemia (6%), and lymphopenia (6%). Median PFS was 6.9 months (95% CI, 3.7-12.5 months) and the overall tumor response rate was 5% (95% CI, 1-13%). The majority of patients (61%) had stable disease as their best overall tumor response.ConclusionsSafety and efficacy results were comparable to those of the RECORD-1 trial. Everolimus is generally well tolerated and provides clinical benefit to Chinese patients with anti-VEGF-refractory mRCC.Trial registrationclinicaltrials.gov, NCT01152801

The efficacy and safety of everolimus for the treatment of progressive gastroenteropancreatic neuroendocrine tumors: A multi‐institution observational study in Taiwan

“…The most significant adverse events (grade 3 or higher) described in two other studies of everolimus treatment in Chinese and Korean patients with metastatic renal cell carcinoma were hyperglycemia, hypertriglyceridemia, anemia, elevated liver enzyme levels, hyponatremia, dyspnea and mucositis . By comparison, the adverse events in our study were generally mild and tolerable.…”

Phosphorylation of mTOR and S6RP predicts the efficacy of everolimus in patients with metastatic renal cell carcinoma

“…The detailed inclusion and exclusion criteria for mRCC patients who participated in the everolimus trial were described previously for NCT01152801 [8]. In the present study, we extracted the data at our single center (Peking University Cancer Hospital and Institute, Beijing) from this phase Ib clinical trial of everolimus.…”

“…We have conducted an open-label phase 1b study of everolimus in Chinese patients with mRCC resistant to VEGFR tyrosine kinase inhibitor (TKI) therapy, suggesting that everolimus is generally well tolerated and provides clinical benefit to Chinese patients with anti-VEGF-refractory mRCC [8]. However, predictive biomarkers for future selection of patients who may benefit from everolimus have not been identified.…”

Axitinib versus sorafenib as a second-line therapy in Asian patients with metastatic renal cell carcinoma: results from a randomized registrational study

“…The availability of Asian-specific safety and efficacy data from a randomized clinical trial comparing one targeted agent versus another is obviously an important factor for making the decision to use a targeted agent in Asian populations. However, most of the available Asian-specific data come from single-arm Phase II, expanded access, or retrospective clinical studies 4–7,11–16,19…”