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Targeted therapies linked to modest survival benefit for elderly patients with renal cell carcinoma
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Targeted therapies appeared associated with modest improvements in OS compared with nontargeted therapies among elderly patients with metastatic renal cell carcinoma, according to results of a retrospective study published in JAMA Network Open.
“Our findings suggest that targeted therapies offered new treatment options to elderly and medically complex patients who may have otherwise foregone the treatments available 15 years ago, given their high toxicity and limited benefit,” Jalpa A. Doshi, PhD, professor of medicine at Perelman School of Medicine at University of Pennsylvania, said in a press release. “Renal cell carcinoma 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 FDA has approved 12 targeted therapies for advanced renal cell carcinoma since 2005 that demonstrated an ability to extend survival in clinical trials with greater tolerability than older treatments. However, the extent of real-world survival benefits from targeted therapies for this patient population remained unclear.
Doshi and colleagues used SEER-Medicare data from 2000 to 2013 to analyze 1,015 patients with stage IV clear cell renal cell carcinoma (mean age, 71.2 years; 39% women) who received targeted (n = 641) or nontargeted (n = 374) therapy. A higher percentage of patients in the targeted therapy group were aged 75 years or older (41% vs. 34%). These patients also had higher comorbidity index and disability scores than those in the nontargeted therapy group.
Researchers estimated the survival advantages of targeted treatments through instrumental variable analysis that controlled for measured and unmeasured cofounders.
OS and renal cell carcinoma-specific survival served as the study’s primary endpoints.
Median follow-up after the first treatment was 8 months (interquartile range, 3-20). During follow-up, 562 patients in the targeted therapy group and 369 patients in the nontargeted therapy group died of any cause.
The rate of death specifically due to renal cell carcinoma was 62% (n = 395) in the targeted therapy group and 76% (n = 283) in the nontargeted therapy group. Unadjusted Kaplan-Meier curves showed patients in the targeted vs. nontargeted therapy group had longer OS (P = .02) and renal cell carcinoma-specific survival (P = .001), but the difference in median OS was not statistically significant (8.7 months vs. 7.2 months).
However, instrumental variable analyses showed a statistically significant median OS advantage of 3 months (95% CI, 0.7-5.3) with targeted therapy, with comparable gains in median renal cell carcinoma-specific survival (unadjusted, 2.7 months; adjusted, 4.9 months).
These analyses revealed significant improvement in OS in the targeted vs. nontargeted therapy group at 1 year (44% vs. 36%; P = .01), 2 years (25% vs. 18%; P = .009) and 3 years (15% vs. 10%; P = .01). Researchers also observed significantly higher rates of renal cell carcinoma-specific survival with targeted therapy at 1 year (55% vs. 47%; P = .02), 2 years (36% vs. 28%; P = .02) and 3 years (25% vs. 18%; P = .02).
Overall, receipt of targeted therapy lower risk for death (HR = 0.78; 95% CI, 0.65-0.94) and for renal cell carcinoma-specific death (HR = 0.77; 95% CI, 0.62-0.96) compared with nontargeted therapy.
A specific focus on the Medicare population, producing results that may not apply to younger or healthier populations, served as the study’s primary limitation. Researchers also did not have access to all the details of patient treatment regimens.
However, “the more sophisticated statistical methods allowed us to see an unbiased picture of how the treatments compared in the real world,” Pengxiang Li, PhD, senior research investigator at Perelman School of Medicine at University of Pennsylvania, said in the release. “The method helped control for unmeasured differences between the treatment groups, which cannot be adjusted using traditional approaches.”
The most important aspect of this study was the high number of patients with metastatic renal cell carcinoma excluded because they did not receive treatment in the 10-year period analyzed by the researchers, Alex Shteynshlyuger, MD, urologist affiliated with New York Urology Specialists, wrote in an accompanying editorial.
“Older patients and those with worse performance status tend to be underrepresented in oncological randomized clinical trials,” Shteynshlyuger said. “[This study] confirms the relevance of data from randomized clinical trials to older and sicker patients. Patients who are older and sicker than patients typically enrolled in randomized clinical trials, when treated with targeted therapy, experienced longer OS compared with those treated with nontargeted therapies, confirming the applicability of findings from [randomized trials] to this population.” – by John DeRosier
Disclosures: Doshi reports consultant/advisory roles with Allergan, Ironwood Pharmaceuticals, Janssen, Kite Pharma, Merck, Otsuka, Regeneron, Sarepta, Sage Therapeutics, Sanofi, Shire and Vertex; research funding from AbbVie, Biogen, Humana, Janssen, Novartis, Pfizer, Pharmaceutical Research and Manufacturers of America, Regeneron, Sanofi and Valeant; and stock held by her spouse in Merck and Pfizer. Li reports consultant payments from Avalon Health Economics, HealthStatistics and Robert Ohsfeldt LLC outside the submitted work. Please see the study for all other authors’ relevant financial disclosures. Shteynshlyuger reports no relevant financial disclosures.
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