Indirect comparisons suggest that of available agents, cabozantinib or nivolumab plus ipilimumab may be the most effective first-line treatment for metastatic renal-cell carcinoma.
There are eight first-line therapies approved for such patients, but there is limited comparative data on these options, Dr. Zachary Klaassen of the University of Toronto, in Canada, and colleagues note in European Urology, online April 13.
The team conducted a systematic review of 37 trials involving more than 13,000 patients and a network meta-analysis on 10 phase 2 and 3 trials involving 4,819 patients. Among agents studied were atezolizumab plus bevacizumab, cabozantinib, pazopanib plus everolimus, sunitinib, sorafenib and nivolumab plus ipilimumab.
"A network meta-analysis," Dr. Klaassen told Reuters Health by email, "allows for important, quick indirect comparisons of treatment regimens using a common comparator across different clinical trials. This is advantageous in a disease space that is constantly shifting and where randomized controlled trials (RCTs) can take years for data to mature."
Via the meta-analysis and based on the surface under the cumulative ranking curves (SUCRA) of 91%, say the researchers, there was a high likelihood that cabozantinib gave the greatest progression-free survival.
For overall survival, via results in five trials, there was a 48% chance that nivolumab plus ipilimumab was the preferred option. However, the researchers point out that "there was no significant difference when indirectly compared to cabozantinib or the combination of atezolizumab plus bevacizumab."
The combination of nivolumab and ipilimumab had a 67% probability of being the best with regard to prevalence of adverse events.
Nevertheless, the researchers point out that among the many limitations of the study was that "individualized dose adjustment of sunitinib and pazopanib has been shown to improve the efficacy and tolerability of these agents and the included studies considered only the standard dose regime."
Moreover, they stress, indirect analyses "must still be acknowledged as a surrogate for head-to-head treatment comparison."
Dr. Klaassen observed that "nivolumab plus ipilimumab and cabozantinib have emerged as the first-line agents of choice based on our analysis. Medication availability and insurance coverage based on jurisdiction, in addition to the patient-physician's goals in treatment . . . will likely guide treatment choice."
He added, "Sunitinib is likely an inappropriate control arm for future RCTs given the performance of nivolumab plus ipilimumab and cabozantinib in our study."
Dr. Robert A. Figlin of Cedars-Sinai Medical Center, in Los Angeles, told Reuters Health by email, "Evidence-based algorithms for the frontline therapy of renal-cell carcinoma continue to evolve. With the recent approvals of ipilimumab/nivolumab in intermediate/poor prognosis patients, and cabozantinib demonstrating superior results compared to sunitinib in intermediate/poor prognosis patients, we have two sets of data without the ability for cross-trial comparisons."
Dr. Figlin, chair of hematology oncology, added, "For good-prognosis patients we still have evidence that sunitinib and pazopanib are the preferred choices. Individualized therapy in the frontline setting will depend on a patient's risk tolerance, co-morbidities, the familiarity of the treating physician with side effect management, and the overall goals of therapy."
SOURCE: https://bit.ly/2HZkHaS
Eur Urol 2018.
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