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Benefit Seen With Targeted Therapies in Elderly and Medically Complex Patients With Metastatic RCC

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Key Points

  • The initial analysis found no statistically significant difference in survival between targeted and nontargeted therapies. However, a more in-depth analysis known as an instrumental variable analysis revealed a 3-month survival advantage with targeted therapies compared to older treatments.
  • Estimated overall survival improvements with targeted therapy vs nontargeted therapies were also statistically significant—8% at 1 year, 7% at 2 years, and 5% at 3 years.
  • Receipt of targeted therapy was associated with a lower hazard of death compared with nontargeted therapy.

Many elderly and medically complex patients with metastatic renal cell carcinoma (RCC)—who are often underrepresented in clinical trials—saw overall survival benefits from treatment with targeted therapies, according to a study that analyzed 13 years of data on Medicare patients published by Li et al in JAMA Network Open. 

Study Background and Methods

Since 2005, the U.S. Food and Drug Administration has approved 12 targeted therapies for the treatment of advanced RCC. However, clinical trials investigating these therapies often exclude more medically complex patients and those over the age of 65 years, leaving a gap in knowledge about the effectiveness of newer vs older treatments in this population, especially when they are treated in routine health-care settings rather than in research studies.

“Our findings suggest that targeted therapies offered new treatment options to elderly and medically complex patients who may have otherwise forgone the treatments available 15 years ago given their high toxicity and limited benefit,” said senior study author Jalpa A. Doshi, PhD, Professor of Medicine in the Perelman School of Medicine at the University of Pennsylvania, Philadelphia. “RCC is a cancer where people can often try other treatment options if the first one isn’t effective, so even small gains may mean that a person might live long enough to try the next innovation. What’s more, studies are showing that current treatments, including immunotherapies, are leading to even better outcomes than those that were observed during our study time frame.”

The researchers conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2000 to 2013 to examine overall survival and estimated overall survival improvements in 1,015 patients with stage IV clear cell RCC who received any FDA-approved targeted therapy (63% of patients) or nontargeted therapy (37%). Most patients were aged 65 years or older, and approximately 13% were younger but eligible for Medicare due to disability prior to their RCC diagnosis.

Results

The initial analysis found no statistically significant difference in survival between targeted and nontargeted therapies. However, a more in-depth analysis that used statistical techniques to mimic the more controlled conditions found in clinical trials—known as an instrumental variable analysis—revealed a 3-month survival advantage with targeted therapies compared to older treatments. Estimated overall survival improvements with targeted therapy vs nontargeted therapies were also statistically significant—8% at 1 year, 7% at 2 years, and 5% at 3 years. Receipt of targeted therapy was associated with a lower hazard of death compared with nontargeted therapy.

“The more sophisticated statistical methods allowed us to see an unbiased picture of how the treatments compared in the real world,” said first study author Pengxiang Li, PhD, Senior Research Investigator at Penn Medicine. “The method helped control for unmeasured differences between the treatment groups, which cannot be adjusted using traditional approaches.”

The study authors concluded, “Targeted therapies were associated with modest survival advantages despite a treatment group with more medical complexity, likely reflecting appropriateness for an expanded population of patients. As advances in cancer treatment continue, rigorous methods that account for unobserved confounders will be needed to evaluate their real-world impact on outcomes.”

Disclosure: For full disclosures of the study authors, visit jamanetwork.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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