Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib Journal Article
| Authors: | Rini, B. I.; Cohen, D. P.; Lu, D. R.; Chen, I.; Hariharan, S.; Gore, M. E.; Figlin, R. A.; Baum, M. S.; Motzer, R. J. |
| Article Title: | Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib |
| Abstract: | Background Hypertension (HTN) is an on-target effect of the vascular endothelial growth factor pathway inhibitor, sunitinib. We evaluated the association of sunitinib-induced HTN with antitumor efficacy and HTN-associated adverse events in patients with metastatic renal cell carcinoma. Methods This retrospective analysis included pooled efficacy (n = 544) and safety (n = 4917) data from four studies of patients with metastatic renal cell carcinoma who were treated with sunitinib 50 mg/d administered on a 4-week-on 2-week-off schedule (schedule 4/2). Blood pressure (BP) was measured in the clinic on days 1 and 28 of each 6-week cycle. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods; hazard ratios (HRs) for survival were also estimated by a Cox proportional hazards models using HTN as a time-dependent covariate. Efficacy outcomes were compared between patients with and without HTN (maximum systolic BP [SBP] ≥140 mm Hg or diastolic BP [DBP] ≥90 mm Hg). Adverse events were also compared between patients with and without HTN (mean SBP ≥140 mm Hg or mean DBP ≥90 mm Hg). All P values were two-sided. Results Patients with metastatic renal cell carcinoma and sunitinib-induced HTN defined by maximum SBP had better outcomes than those without treatment-induced HTN (objective response rate: 54.8% vs 8.7%; median PFS: 12.5 months, 95% confidence interval [CI] = 10.9 to 13.7 vs 2.5 months, 95% CI = 2.3 to 3.8 months; and OS: 30.9 months, 95% CI = 27.9 to 33.7 vs 7.2 months, 95% CI = 5.6 to 10.7 months; P <. 001 for all). Similar results were obtained when comparing patients with vs without sunitinib-induced HTN defined by maximum DBP. In a Cox proportional hazards model using HTN as a time-dependent covariate, PFS (HR of disease progression or death =. 603, 95% CI =. 451 to. 805; P <. 001) and OS (HR of death =. 332, 95% CI =. 252 to. 436; P <. 001) were improved in patients with treatment-induced HTN defined by maximum SBP; OS (HR of death =. 585, 95% CI =. 463 to. 740; P <. 001) was improved in patients with treatment-induced HTN defined by maximum DBP, but PFS was not. Few any-cause cardiovascular, cerebrovascular, ocular, and renal adverse events were observed. Rates of adverse events were similar between patients with and without HTN defined by mean SBP; however, hypertensive patients had somewhat more renal adverse events (5% vs 3%; P =. 013). Conclusions In patients with metastatic renal cell carcinoma, sunitinib-associated HTN is associated with improved clinical outcomes without clinically significant increases in HTN-associated adverse events, supporting its viability as an efficacy biomarker. © The Author 2011. |
| Keywords: | adult; treatment outcome; major clinical study; overall survival; sunitinib; drug efficacy; drug safety; heart left ventricle failure; hypertension; side effect; metastasis; progression free survival; kidney failure; antineoplastic activity; kidney carcinoma; acute kidney failure; heart failure; heart infarction; transient ischemic attack; blood pressure; visual disorder; brain hematoma; congestive heart failure; proteinuria; thrombotic thrombocytopenic purpura; nephrotic syndrome; blurred vision; visual acuity; posterior reversible encephalopathy syndrome; visual field defect |
| Journal Title: | JNCI: Journal of the National Cancer Institute |
| Volume: | 103 |
| Issue: | 9 |
| ISSN: | 0027-8874 |
| Publisher: | Oxford University Press |
| Date Published: | 2011-05-04 |
| Start Page: | 763 |
| End Page: | 773 |
| Language: | English |
| DOI: | 10.1093/jnci/djr128 |
| PROVIDER: | scopus |
| PMCID: | PMC3086879 |
| PUBMED: | 21527770 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 23 June 2011" - "CODEN: JNCIA" - "Source: Scopus" |
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