Journal of the National Cancer Institute Advance Access published online on October 7, 2008
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djn319
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ARTICLES |
Sorafenib for Older Patients With Renal Cell Carcinoma: Subset Analysis From a Randomized Trial
Affiliations of authors: The Royal Marsden Hospital NHS Trust, Sutton, Surrey, UK (TE); Hopital European Georges Pompidou, Paris, France (SO); Central Clinical Hospital of Military Medical Academy, Warsaw, Poland (CS); Institut Paoli-Calmettes, Marseille, France (GG); Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany (HH); University of Utah, School of Medicine, Urology Clinical Research, Salt Lake City, UT (RM); Bayer Pharmaceuticals, West Haven, CT (FC, SA, SS); Cleveland Clinic Cancer Center, Cleveland, OH (RB); Institut Gustave Roussy, Villejuif, France (BE)
Correspondence to: Tim Eisen, PhD, FRCP, Department of Oncology (R4), Box 193, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK (e-mail: tgqe2{at}cam.ac.uk).
Background: The perception that older cancer patients may be at higher risk than younger patients of toxic effects from cancer therapy but may obtain less clinical benefit from it may be based on the underrepresentation of older patients in clinical trials and the known toxic effects of cytotoxic chemotherapy. It is not known how older patients respond to targeted therapy.
Methods: This retrospective subgroup analysis of data from the phase 3, randomized Treatment Approach in Renal Cancer Global Evaluation Trial examined the safety and efficacy of sorafenib in older (age 
70 years, n = 115) and younger patients (age <70 years, n = 787) who received treatment for advanced renal cell carcinoma. Patient demographics and progression-free survival were recorded. Best tumor response, clinical benefit rate (defined as complete response plus partial response plus stable disease), time to self-reported health status deterioration, and toxic effects were assessed by descriptive statistics. Health-related quality of life was assessed with a Cox proportional hazards model. Kaplan–Meier analyses were used to summarize time-to-event data.
Results: Median progression-free survival was similar in sorafenib-treated younger patients (23.9 weeks; hazard ratio [HR] for progression compared with placebo = 0.55, 95% confidence interval [CI] = 0.47 to 0.66) and older patients (26.3 weeks; HR = 0.43, 95% CI = 0.26 to 0.69). Clinical benefit rates among younger and older sorafenib-treated patients were also similar (83.5% and 84.3%, respectively) and were superior to those of younger and older placebo-treated patients (53.8% and 62.2%, respectively). Adverse events were predictable and manageable regardless of age. Sorafenib treatment delayed the time to self-reported health status deterioration among both older patients (121 days with sorafenib vs 85 days with placebo; HR = 0.66, 95% CI = 0.43 to 1.03) and younger patients (90 days with sorafenib vs 52 days with placebo; HR = 0.69, 95% CI = 0.59 to 0.81) and improved quality of life over that time.
Conclusions: Among patients with advanced renal cell carcinoma receiving sorafenib treatment, outcomes of older (70 years) and younger (<70 years) patients were similar.
| CONTEXT AND CAVEATS Prior knowledge It was not known how older patients would respond to molecularly targeted therapy. Study design
Retrospective subgroup analysis of data from a phase 3 randomized trial that examined the safety and efficacy of sorafenib in 115 older (age Contribution Median progression-free survival and clinical benefit rates (ie, complete response + partial response + stable disease) were similar in younger and older sorafenib-treated patients and better than those of younger and older placebo-treated patients. Adverse effects were predictable and manageable regardless of age. Sorafenib treatment delayed the time to self-reported health status deterioration in both groups and improved quality of life over that time. Implications Results of this study support the use of sorafenib as a treatment for advanced renal cell carcinoma in all age groups. Limitations The study was not designed to test for statistically significant differences between treatment effects in younger and older subgroups. The sample size in the older group was limited, and there was an imbalance in treatment assignments in the older group. Older patients who participate in clinical trials are generally healthier than those who do not participate, and so results of this study may not be generalizable. From the Editors
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Manuscript received March 5, 2008; revised July 25, 2008; accepted August 4, 2008.
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J Natl Cancer Inst 2008 100: 1417.
J Natl Cancer Inst 2008 100: 1417.