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

For all author emails, please log on.

Citation and License

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

Published: 21 March 2013



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.


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.


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.


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, NCT01152801

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