RECORD-4 prospectively evaluated efficacy and safety of EVE in pts with mRCC who progressed on first-line treatment with an anti-VEGF or a cytokine agent. Here we present outcomes in Asian versus (vs) non-Asian pts.
Adult pts (≥ 18 years) with clear cell mRCC were enrolled into 1 of 3 cohorts based on prior first-line therapy: sunitinib, other anti-VEGF (sorafenib, bevacizumab, pazopanib, other), or cytokines. Pts received EVE 10 mg/d until progression of disease (RECIST, v1.0) or intolerance. The primary endpoint was PFS by investigator review. Data cutoff: Sept 1, 2014.
Among Asian (n = 55) vs non-Asian (n = 79) pts, 98% vs 84% had good/intermediate MSKCC prognosis; 73% vs 65% were men, and 85% vs 73% were <65 years of age. All (100%) Asian pts were of Chinese ethnicity. Median duration of exposure was 5.5 mo for Asian and 6.0 mo for non-Asian pts. Among Asian vs non-Asian pts, median PFS (mo, 95% CI) was 7.4 (5.5-11.0) vs 7.8 (5.3-12.9) overall, 7.4 (3.7-12.8) vs 4.0 (2.5-12.9) with prior sunitinib, 5.7 (3.6-11.0) vs 9.2 (5.5-18.0) with prior other anti-VEGFs, and 16.5 (1.9-not estimable [NE]) vs 12.9 (2.6-NE) with prior cytokines. Clinical benefit rate was similar between populations: 74.5% (95% CI, 61.0-85.3) for Asian pts and 74.7% (95% CI, 63.6-83.8) for non-Asian pts. Most pts achieved stable disease as best overall response (Asian, 63.6%; non-Asian, 69.6%). Overall rate of grade 3/4 adverse events (AEs) appeared similar for Asian (58%) and non-Asian pts (54%). Most frequently reported grade 3/4 AEs (incidences ≥5% in the overall population) for Asian vs non-Asian pts were stomatitis/mouth ulceration (11% vs 5%), anemia (7% vs 17%), hypertriglyceridemia (5% vs 4%), decreased hemoglobin (5% vs 0), proteinuria (5% vs 1%), respiratory failure (5% vs 1%), and hyperglycemia (4% vs 5%).
Second-line EVE demonstrated comparable efficacy and AE profiles in Asian and non-Asian pts. Efficacy and safety outcomes by prior therapy should be interpreted with caution because of small pt numbers in some subpopulations.
Clinical trial identification
A. Alyasova: consulting physician for Novartis and compensation from Novartis for consulting and research support and business travel. D. Ye: Novartis Investigator but no compensation received. B. Alekseev: research funding by Astellas, Johnson and Johnson and Novartis; compensation from Sanofi, Johnson and Johnson and Novartis for consulting or advisory role. L. Xie: clinical trial principle investigator for Ipsen Pharma Biotech. R.D. Kowalyszyn: compensation from Novartis, Eli Lilly, Glaxo Smith Kline, Roche and Elea for research funding; compensation from Merck Sharp Dohme and Novartis for consulting and speaker's bureau. O. Karyakin: employed by Medical Radiological Research Center. Y.V. NerÃ³n: research funding from Active Biotech, Amgen, Astellas, Blau FarmacÃªutica, Genentech, Glaxo Smith Kline, Novartis, Roche, Tesaro. T.M. Cosgriff: Stockholder in Enanta and Alexion. Employed by Lakeside Hospice. L. Collins: A Novartis Pharmaceutical Corporation employee. T. Brechenmacher, J.C. Lin, L. Morgan: Novartis employee. R. Motzer: grants and personal fees from Novartis, during the conduct of the study; grants and personal fees from Pfizer, grants and personal fees from GlaxoSmithKline, grants from Genentech, grants from GlaxoSmithKline, outside the submitted work. All other authors have declared no conflicts of interest.