Sorafenib for older patients with renal cell carcinoma: subset analysis from a randomized trial

Abstract

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 >or=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 (>or=70 years) and younger (<70 years) patients were similar.

Figure 1

CONSORT trial flow diagram. Patient enrollment and outcomes are shown for all patients with renal cell carcinoma (aged <70 or ≥70 y) who were randomly assigned to treatment with sorafenib or placebo. An intent-to-treat analysis was used.

Figure 2

Progression-free survival by age (<70 or ≥70 y) among patients with renal cell carcinoma who were treated with sorafenib or with placebo. The median survival and 95% confidence interval (CI) are shown as well as the hazard ratios (HRs) that compare progression in the sorafenib treatment group with that in the placebo treatment group. Sor = sorafenib; Pla = placebo.

Figure 3

Time to self-reported health status deterioration by age according to treatment (sorefenib vs placebo) as measured by the Functional Assessment of Cancer Therapy–Kidney Cancer Symptom Index (FKSI). A) Patients aged ≥70 y. B) Patients aged <70 y. The median time to self-reported health status deterioration and 95% confidence interval (CI) is shown as well as the hazard ratios (HRs) that compare self-reported health status deterioration in the sorafenib treatment group with that in the placebo treatment group. Sor = sorafenib; Pla = placebo.

Figure 4

Time to self-reported health status deterioration by age according to treatment (sorefenib vs placebo) as measured by the Physical Well-Being (PWB) domain of Functional Assessment of Cancer Therapy–General. A) Patients aged ≥70 y. B) Patients aged <70 y. The median time to self-reported health status deterioration and 95% confidence interval (CI) is shown as well as the hazard ratios (HRs) that compare self-reported health status deterioration in the sorafenib treatment group with that in the placebo treatment group. Sor = sorafenib; Pla = placebo.