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

Jun Guo, Yiran Huang, Xu Zhang, Fangjian Zhou, Yinghao Sun, Shukui Qin, Zhangqun Ye, Hui Wang, Annette Jappe, Patrick Straub, Nicoletta Pirotta, Sven Gogov, Jun Guo, Yiran Huang, Xu Zhang, Fangjian Zhou, Yinghao Sun, Shukui Qin, Zhangqun Ye, Hui Wang, Annette Jappe, Patrick Straub, Nicoletta Pirotta, Sven Gogov

Abstract

Background: In 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.

Methods: An 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.

Results: A 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.

Conclusions: Safety 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 registration: clinicaltrials.gov, NCT01152801.

Figures

Figure 1
Figure 1
Kaplan-Meier estimate of progression-free survival. The plot depicts the probability of progression-free survival over time (months) for patients who received everolimus (full analysis set population). The square symbol represents censoring times. The number of patients still at risk is shown for each time point.
Figure 2
Figure 2
Kaplan-Meier estimate of overall survival. The plot depicts the probability of overall survival over time (months) for patients who received everolimus. The square symbol represents censoring times. The number of patients still at risk is shown for each time point.

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