Outcomes based on plasma biomarkers in METEOR, a randomized phase 3 trial of cabozantinib vs everolimus in advanced renal cell carcinoma (vol 21, 904, 2021)

被引：1

作者：

Powles, Thomas ^{[1
]}

Choueiri, Toni K. ^{[2
]}

Motzer, Robert J. ^{[3
]}

Jonasch, Eric ^{[4
]}

Pal, Sumanta ^{[5
]}

Tannir, Nizar M. ^{[4
]}

Signoretti, Sabina ^{[6
]}

Kaldate, Rajesh ^{[7
]}

Scheffold, Christian ^{[7
]}

Wang, Evelyn ^{[7
]}

Aftab, Dana T. ^{[7
]}

Escudier, Bernard ^{[8
]}

George, Daniel J. ^{[9
]}

机构：

[1] Queen Mary Univ London, Barts Canc Inst, London, England

[2] Dana Farber Canc Ctr, Boston, MA USA

[3] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA

[4] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[5] City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA

[6] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA

[7] Exelixis Inc, Alameda, CA USA

[8] Gustave Roussy, Villejuif, France

[9] Duke Canc Inst, Durham, NC USA

来源：

BMC CANCER | 2021年 / 21卷 / 01期

关键词：

Biomarker; Cabozantinib; Everolimus; METEOR; Renal cell carcinoma;

D O I：

10.1186/s12885-021-08693-9

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: In the phase 3 METEOR trial, cabozantinib improved progression-free survival (PFS) and overall survival (OS) versus everolimus in patients with advanced RCC after prior antiangiogenic therapy. Methods: In this exploratory analysis, plasma biomarkers from baseline and week 4 from 621 of 658 randomized patients were analyzed for CA9, HGF, MET, GAS6, AXL, VEGF, VEGFR2, and IL-8. PFS and OS were analyzed by baseline biomarker levels as both dichotomized and continuous variables using univariate and multivariable methods. For on-treatment changes, PFS and OS were analyzed using fold change in biomarker levels at week 4. Biomarkers were considered prognostic if p < 0.05 and predictive if pinteraction < 0.05 for the interaction between treatment and biomarker. Results: Hazard ratios for PFS and OS favored cabozantinib versus everolimus for both low and high baseline levels of all biomarkers (hazard ratios ≤0.78). In univariate analyses, low baseline HGF, AXL, and VEGF were prognostic for improvements in both PFS and OS with cabozantinib, and low HGF was prognostic for improvements in both PFS and OS with everolimus. Low AXL was predictive of relative improvement in PFS for cabozantinib versus everolimus. Results were generally consistent when baseline biomarkers were expressed as continuous variables, although none were predictive of benefit with treatment. In multivariable analysis, low baseline HGF was independently prognostic for improved PFS for both cabozantinib and everolimus; low HGF, GAS6, and VEGF were independently prognostic for improved OS with cabozantinib. No biomarkers were independently prognostic for OS with everolimus. On-treatment increases in some biomarkers appeared prognostic for PFS or OS with cabozantinib in univariate analyses; however, none were independently prognostic in multivariable analysis. Conclusions: PFS and OS were improved with cabozantinib versus everolimus at high and low baseline levels of all biomarkers. Low baseline HGF was consistently identified as a prognostic biomarker for improved PFS or OS with cabozantinib or everolimus, supporting further prospective evaluation of the prognostic significance of HGF in advanced RCC. Trial registration: ClinicalTrials.gov NCT01865747 (registered on 05/31/2013). © 2021, The Author(s).

引用

页数：2