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Open Access Research article

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 Guo1*, Yiran Huang2, Xu Zhang3, Fangjian Zhou4, Yinghao Sun5, Shukui Qin6, Zhangqun Ye7, Hui Wang8, Annette Jappe9, Patrick Straub10, Nicoletta Pirotta11 and Sven Gogov12

Author affiliations

1 Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Beijing, 100142, China

2 Shanghai Renji Hospital, Shanghai, China

3 The General Hospital of PLA, Beijing, China

4 Sun Yat-sen University Cancer Center, Guangzhou, China

5 Shanghai Changhai Hospital, Yangpu District, China

6 Nanjing Bayi Hospital, Yanggongjing, Nanjing, China

7 Wuhan Tongji Hospital, Wuhan, China

8 Beijing Novartis Pharma Company, Ltd., Beijing, China

9 Novartis Pharma AG, Basel, Switzerland

10 Novartis Pharma AG, Basel, Switzerland

11 Novartis Pharma AG, Basel, Switzerland

12 Novartis Pharma AG, Basel, Switzerland

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Citation and License

BMC Cancer 2013, 13:136  doi:10.1186/1471-2407-13-136

Published: 21 March 2013

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

Keywords:
Asian; Everolimus; mTOR inhibitor; Renal cell cancer; Sunitinib; Sorafenib