RECORD-4 multicenter phase 2 trial of second-line everolimus in patients with metastatic renal cell carcinoma: Asian versus non-Asian population subanalysis

Abstract

Background: RECORD-4 assessed everolimus in patients with metastatic renal cell carcinoma (mRCC) who progressed after 1 prior anti-vascular endothelial growth factor (VEGF) or cytokine and reinforced the clinical benefit of second-line everolimus. Because of the high percentage of patients from China enrolled in RECORD-4 (41%) and some reported differences in responses to certain targeted agents between Chinese and Western patients, this subanalysis evaluated outcomes in Asian versus non-Asian patients.

Methods: RECORD-4 enrolled patients with clear cell mRCC into 3 cohorts based on prior first-line therapy: sunitinib, other anti-VEGF (sorafenib, bevacizumab, pazopanib, other), or cytokines. Patients received everolimus 10 mg/d until progression of disease (RECIST, v1.0) or intolerance. Primary end point was progression-free survival per investigator review. Data cutoff was Sept 1, 2014.

Results: Among Asian (n = 55) versus non-Asian (n = 79) patients, 98% versus 84% had good/intermediate MSKCC prognosis; 73% versus 65% were men, and 85% versus 73% were < 65 years of age. All (100%) Asian patients were of Chinese ethnicity. Median duration of exposure was 5.5 mo for Asian and 6.0 mo for non-Asian patients. Among Asian versus non-Asian patients, median progression-free survival (months) was 7.4 versus 7.8 overall, 7.4 versus 4.0 with prior sunitinib, and 5.7 versus 9.2 with prior other anti-VEGFs. Clinical benefit rate was similar between populations: 74.5% (95% CI 61.0-85.3) for Asian patients and 74.7% (95% CI 63.6-83.8) for non-Asian patients. Most patients achieved stable disease as best overall response (Asian, 63.6%; non-Asian, 69.6%). Overall rate of grade 3/4 adverse events appeared similar for Asian (58%) and non-Asian patients (54%).

Conclusions: This RECORD-4 subanalysis demonstrated comparable efficacy and adverse event profiles of second-line everolimus in Asian and non-Asian patients. Efficacy and safety outcomes by prior therapy should be interpreted with caution because of small patient numbers in some subpopulations.

Trial registration: Everolimus as Second-line Therapy in Metastatic Renal Cell. Carcinoma (RECORD-4); ClinicalTrials.gov identifier: NCT01491672 . Registration date: December 14, 2011.

Keywords: Asians; Clear-cell metastatic renal cell carcinoma; Ethnicity; Everolimus; Sequence.

Conflict of interest statement

Authors’ information

not applicable.

Ethics approval and consent to participate

The study was conducted in accordance with the International Conference on Harmonisation Good Clinical Practice guidelines, and approved by institutional review boards or independent ethics committees at each center. All patients provided written informed consent.

Consent for publication

not applicable.

Competing interests

AA received compensation from Novartis for research. AR and LD are employees of Novartis Pharmaceuticals Corp. RJM received compensation from Novartis, BMS, Pfizer, Genentech/Roche and Eisai for research and from Novartis, Pfizer, and Eisai for consulting. LY and DY have declared no competing interests.

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Figures

Fig. 1

Progression-free survival (PFS) in the Asian and non-Asian populations (a), and by first-line treatment cohorts in the Asian and non-Asian populations for (b) sunitinib, (c) other anti-VEGF agents, and (d) cytokines. CI=confidence interval; K-M=Kaplan-Meier; NE=not estimable; PFS=progression-free survival; VEGF=vascular endothelial growth factor