Targeted therapies linked to survival benefits for older patients with advanced renal cancer

By Marilynn Larkin

NEW YORK (Reuters Health) - 21/6/2019

Targeted therapies were associated with "modest survival advantages" in elderly Medicare patients with metastatic renal cell carcinoma (mRCC) in a retrospective study.

"With the earlier, more toxic therapies, people who were older or medically complex were not always good candidates for treatment," Dr. Jalpa Doshi of the University of Pennsylvania told Reuters Health by email. "Our study confirmed that a broader range of patients have been able to receive targeted therapies and to extend their survival. This is important, because sometimes a treatment with even modest benefit can allow a person to live long enough to take advantage of future treatment innovations."

"Outcomes were less impressive in the real world compared to what had been found in clinical trials, probably because the treatment group was older and sicker," she added.

Dr. Doshi and colleagues analyzed Surveillance, Epidemiology, and End Results (SEER) data from 2000 to 2013 on patients with mRCC who received targeted or nontargeted therapy at the time of diagnosis.

As reported online June 14 in JAMA Network Open, 1,015 patients (mean age 71.2, 39% women) were included, of whom 63% received targeted therapy.

The targeted therapy group had a greater percentage of patients who were disabled (i.e., <65 years old but eligible for Medicare because of disability), older (at least 75) and with a higher comorbidity index and disability scores compared with the nontargeted therapy group.

Unadjusted Kaplan-Meier survival curves showed higher overall survival for targeted versus nontargeted therapy, although median survival was not statistically significantly different between the groups (8.7 months vs. 7.2 months).

However, the instrumental variable analysis showed a median overall survival advantage of three months and statistically significant overall survival improvements associated with targeted therapy: 8% at one year (44% vs. 36%), 7% at two years (25% vs.18%), and 5% at three years (15% vs. 10%).

Further, receipt of targeted therapy was associated with a lower hazard of death (overall survival hazard ratio, 0.78; RCC-specific survival HR, 0.77).

"To our knowledge, this is the first observational comparative effectiveness study of targeted vs nontargeted therapy for mRCC using an instrumental variable approach to control for both observed and unobserved confounders," the authors state. "In keeping with clinical trial results, we found that the use of targeted therapy was associated with longer overall survival and RCC-specific survival compared with the use of nontargeted therapy among Medicare beneficiaries who received a diagnosis of mRCC."

Dr. Doshi said, "Our findings highlight that it's important to use the right methods to evaluate treatments in the real world, where many factors can influence cancer treatment outcomes. Simple comparisons didn't detect differences, but more rigorous methods revealed the advantages of targeted therapies. It's important to pay attention to the research methods being applied, not just the conclusions."

Dr. Alex Shteynshlyuger of New York Urology Specialists in New York City, author of a related editorial, commented by email, "Integrating the results of this study with our knowledge about the comparative effectiveness of newer therapy such as nivolumab plus ipilimumab suggests that many older patients can derive significant benefit from treatment."

"Yet we know (many) older patients received no treatment, many of whom may have benefited from targeted therapy for renal cell carcinoma," he told Reuters Health. "This is of significant concern as treating physicians may underestimate the benefits of treatment in the elderly and give too much weight to treatment risks in the risk-benefit analysis."

"With the significant improvement in life expectancy from cardiovascular disease over the past 20 years, there is a dire need to enroll older and sicker patients in high-quality randomized controlled trials for diseases that affect the elderly," he said. "While there is a consensus that patients need to be part of the shared decision-making about treatment, the only way they can make rational choices that are in their best interest is if they are given facts."

"Without high-quality studies that enroll elderly and sicker patients, even highly experienced physicians have difficulty recommending when the benefit of treatment outweigh the risks," Dr. Shteynshlyuger concluded.


JAMA Netw Open 2019.

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