Targeted therapy showed a greater survival benefit than nontargeted therapy in a real world population of metastatic renal cell carcinoma (RCC) patients, according to the results of a retrospective cohort study recently published in JAMA Network Open. Although the benefit was modest, the results confirm what’s been seen among this patient population in clinical trials.
“For many years we have adapted to [using] targeted therapy instead of these cytokine-based therapies, and we know that in clinical trials, that the targeted therapies are better,” Kai Tsao, MD, Medical Director of the Ruttenberg Treatment Center at Mount Sinai’s Tisch Cancer Institute, told Cancer Network. “But we also know that patients in the real world are not clinical trial candidates and that that benefit is always in question.”
“This [study] validates something that we have known for many years, that targeted therapy is superior to nontargeted, cytokine-based therapy,” Tsao added.
The retrospective cohort study included 1,015 patients who received a diagnosis of stage IV clear cell RCC between 2000 and 2011 and were treated with targeted or nontargeted therapy in the first-line setting. Patient demographic, diagnostic, clinical, and cause-of-death information was obtained through the Surveillance, Epidemiology, and End Results Program cancer registry, which was paired with Medicare enrollment and claims data to collect information about covered health care services.
Overall, 374 patients received nontargeted therapy (interferon or aldesleukin) and 641 patients received targeted therapy. The majority of patients who received targeted therapy were treated with sunitinib (54%), with the next most common being temsirolimus (16%) or sorafenib (15%).
An unadjusted analysis showed a 1.6-month higher overall survival (OS) for patients who received targeted therapy compared with nontargeted therapy (8.7 vs 7.2 months), but the gain lacked statistical significance (P=0.14). In an instrumental variable analysis, the survival gain increased to 3.0 months and was statistically significant (11.8 vs 8.8 months; P=.01).
The instrumental variable approach also showed that patients who received targeted therapy had a 23% decreased likelihood of death from RCC (HR, 0.77), and a higher RCC-specific survival rate compared with nontargeted therapy at 1 year (55% vs 47%), 2 years (36% vs 28%), and 3 years (25% vs 18%), all of which were statistically significant (P=0.02).
By using an instrumental variable approach, Tsao explained, the researchers eliminated some of the biases and saw that the survival benefit became significant. Tsao described the survival benefit as “relatively modest,” but explained that this could be due to several factors, such as the study’s inclusion of patients who are older, have metastatic disease upfront, and have more comorbidities.
In light of the entry of combination targeted and immunotherapies in the first-line treatment setting, he pointed out the limited application of the findings.
“The reality is that, probably, the findings were long overdue and do not matter as much now because we are entering an age where patients are receiving combination targeted plus immunotherapy, or combination immunotherapies right up front,” said Tsao. “In essence, whether there was a realistic benefit is a really dated question because we are now beyond that era.”