Targeted therapy can benefit complex patients with advanced RCC
medwireNews: Targeted therapy improves survival over nontargeted therapy among patients with metastatic renal cell carcinoma (RCC), including those who are older and have disabilities, shows an analysis of real-world data.
Jalpa Doshi (University of Pennsylvania, Philadelphia, USA) and co-investigators say that the “targeted therapies likely offered new options for individuals who might have foregone treatment in the era before targeted therapy because of toxicity concerns, and our results underscore that survival benefits may vary when treatments are administered to a broader population of patients” than typically included in randomized controlled trials (RCTs).
They add: “This finding highlights the need for patient-centered conversations that focus on potential benefits and risks in the context of the diverse personal circumstances, values, and goals of individuals treated in real-world settings.”
The cohort study examined SEER registry and Medicare data for 1015 patients (mean age, 71.2 years; 39% women) diagnosed with stage IV clear cell RCC between 2000 and 2013. Of these, 63% received targeted therapy and 37% received nontargeted therapy.
The researchers found that the targeted therapy group had a higher proportion of disabled patients (<65 years old who were eligible for Medicare because of disability) than the nontargeted therapy group as well as more older patients (≥75 years), greater comorbidity, a higher mean claims-based disability score, and increased levels of fatigue.
During a median 8.0 months of follow-up, the all-cause mortality rates were 88% and 99% among the patients who did and did not recieve targeted therapy, respectively, with corresponding RCC-specific mortality rates of 62% and 76%.
Median unadjusted overall survival (OS; 8.7 vs 7.2 months) and RCC-specific survival (13.2 vs 10.5 months) were longer with targeted versus nontargeted therapy groups, but not significantly so.
However, after accounting for measured and unmeasured confounders, the researchers found that targeted therapy was associated with a median 3.0-month OS advantage and 4.9-month RCC-specific survival advantage, relative to nontargeted therapy.
Furthermore, there were significant improvements in OS with targeted versus nontargeted therapy of 8 percentage points at 1 year (44 vs 36%), 7 percentage points at 2 years (25 vs 18%), and 5 percentage points at 3 years (15 vs 10%).
A similar pattern was seen for RCC-specific survival, and overall, receipt of targeted therapy was associated with a significant 22% reduced risk for death from any cause and a significant 23% reduced risk for death from RCC.
Writing in JAMA Network Open, Doshi and co-authors conclude: “Targeted therapies may have enabled a broader range of patients with metastatic renal cell carcinoma to be treated and were associated with modest survival advantages over nontargeted therapies.”
But they caution that their findings “may not be generalizable to younger or healthier populations.”
In an accompanying commentary, Alex Shteynshlyuger, from New York Urology Specialists in the USA, says that the study “confirms the relevance of data from RCTs to older and sicker patients.”
He also points out that 79% of 9826 potential study participants were excluded from analysis because they received no treatment for metastatic RCC during the study period.
Therefore “[f]urther prospective studies are needed to determine who among the 79% of patients with metastatic RCC who received no treatment would benefit from treatment.”
Shteynshlyuger concludes: “In the meantime, the clinician is left with a greater understanding of outcomes of targeted therapy in older adults that can be incorporated into heuristic models to help in the treatment decisions.”
By Laura Cowen
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