In a randomized, 3-arm, phase 2 trial of patients (pts) with metastatic renal cell carcinoma (mRCC) following 1 VEGF-targeted therapy, LEN+EVE improved median progression-free survival (PFS) compared with EVE (hazard ratio [HR] 0.40; 95% confidence interval [CI] 0.24–0.68; P < 0.001) or LEN (HR 0.66; 95% CI 0.39–1.10; P = 0.121).(Motzer et al. Lancet Oncol 2015) We present biomarker analyses from this study.
Serum samples collected at baseline were analyzed by Luminex-based xMAP® assays for 40 candidate biomarkers. Baseline biomarker levels were correlated with PFS using Cox regression analysis. Biomarkers with the strongest associations (top 5 ranked by log-rank P-value and HR) with PFS in the LEN+EVE arm were integrated into composite biomarker scores (CBS)(Voss et al. Br J Cancer 2016) All P-values are nominal.
Serum samples from 145 pts (LEN+EVE, n = 49; LEN, n = 50; EVE, n = 46) were analyzed. HGF, MIG, IL-18BP, IL-18, and ANG-2 concentrations demonstrated the strongest correlation with PFS and were selected for the CBS analysis. Associations with PFS are summarized in the table. In the LEN+EVE arm, median PFS for pts with high (3–5) vs low (0–2) CBS was 20.1 vs 5.6 months, respectively (HR 0.28; P = 0.002), whereas no significant difference between high vs low CBS was seen in the EVE arm (3.6 vs 5.5 months; HR 1.02; P = 0.951). Median PFS differed significantly between treatment arms for pts with high CBS (LEN+EVE vs EVE, 20.1 vs 3.6 months; P < 0.001), but not for pts with low CBS (LEN+EVE vs EVE, 5.6 vs 5.5 months; P = 0.329).Table: 76P
|LEN+EVE||EVE||LEN+EVE vs EVE HR (95% CI)|
|n||Median PFS (months)||n||Median PFS (months)|
|Total||51||14.6||50||5.5||0.40 (CI 0.24–0.68) P < 0.001|
|High CBS||28||20.1||20||3.6||0.19 (0.09–0.41) P < 0.001|
|Low CBS||20||5.6||24||5.5||0.70 (0.34–1.43) P = 0.329|
|High vs low HR (95% CI)||0.28 (0.12–0.63) P = 0.002||1.02 (0.52–1.99) P = 0.951|
In pts treated with LEN+EVE, high CBS was correlated with PFS benefit; further research is needed to determine if the score can be used to identify pts who may benefit from combination therapy. Altogether, these biomarkers may be predictors of response to LEN+EVE therapy in pts with mRCC.
Clinical trial identification
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Editorial assistance was provided by Oxford PharmaGenesis of Newtown, PA, USA, which was funded by Eisai Inc.
C-H. Lee: Consulting/advisory role: Exelixis; Research funding: Bristol-Myers Squibb, Eisai, Pfizer. R.J. Motzer: Consulting/advisory role: Eisai, Exelixis, Novartis, Pfizer; Research funding: Bristol-Myers Squibb, Eisai, Genentech/Roche, GlaxoSmithKline, Novartis, Pfizer; Travel, accomodations, expenses: Bristol-Myers Squibb. H. Glen: Consulting/advisory role: Astellas Pharma, Eisai, and Janssen; Research funding: Eisai. M.D. Michaelson: Consulting/advisory role: Exelixis, Novartis, Pfizer; Research funding: Argos Therapeutics, Bristol-Myers Squibb, Eisai, Exelixis, Genentech, Merck, Pfizer, Takeda. J. Larkin: Research funding: Pfizer (institution), Novartis (institution), Bristol-Myers Squibb, Merck Sharp & Dohme; Travel, accomodations, expenses: Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Novartis, GlaxoSmithKline, Genentech, Eisai. Y. Minoshima, M. Kanekiyo, R. Dairiki, Y. Funahashi: Employee: Eisai Co., Ltd. P. Sachdev, C.E. Dutcus: Employee: Eisai Inc. M.H. Voss: Honoraria: Novartis; Consulting/advisory role: Alexion Pharmaceuticals, Calithera Biosciences, Exelixis, GlaxoSmithKline, Natera, Novartis, Pfizer; Research funding: Bristol-Myers Squibb, Genentech/Roche, Pfizer; Travel, accommodations, expenses: Novartis, Takeda.