INDIRECT COMPARISONS OF SAFETY OF TARGETED THERAPIES FOR METASTATIC RENAL CELL CARCINOMA- A NETWORK META-ANALYSIS
Author(s)
Heo JH, Park C, Rascati KL
The University of Texas at Austin, Austin, TX, USA
OBJECTIVES: Renal cell carcinoma (RCC) is the most common type of kidney cancer. Disease specific survival for metastatic RCC (mRCC) was significantly improved with the introduction of the targeted agents since 2005. However, there are not enough head-to-head clinical trials comparing the safety between several pairs of targeted therapies. This study aimed to compare toxicity outcomes among targeted agents in patients with mRCC by using network meta-analysis (NMA). METHODS: The PubMed, MEDLINE, Cochrane Library, and Web of Science were searched to identify phase II or III randomized clinical trials (RCTs) of targeted therapies in patients with mRCC published between January 2000 and September 2016. Discontinuation rates due to severe adverse events were compared using risk ratios (RRs) and 95% confidence intervals (CIs). A network of the RCTs involving targeted agents was constructed to conduct the Bayesian NMA. The surface under the cumulative ranking curve (SUCRA) of each treatment was calculated to assess the probability of the best treatment. RESULTS: A total of 11,265 patients with mRCC were included from 28 RCTs. Among the first-line therapy, the RRs of discontinuation were not significantly different among treatments, except that the combination therapy of temsirolimus/bevacizumab was associated with a higher risk of discontinuation due to severe adverse events compared to everolimus, placebo/interferons, and temsirolimus (RR=2.69 (95% CI=1.18-6.13), RR=2.99 (95% CI=1.58-5.66), and RR=3.60 (95% CI=1.40-9.25), respectively). For second-line therapy, axitinib had significantly lower relative risks of discontinuation compared to cabozantinib, everolimus, lenvatinib, and other treatments. In RRs of discontinuation, the largest values of SUCRAs were found in temsirolimus among the first-line therapy (83.1) and axitinib among the second-line therapy (95.1). CONCLUSIONS: Regarding medication safety, temsirolimus and axitinib may be appropriate options in the first-line and second-line therapy in patients with mRCC, respectively.
Conference/Value in Health Info
2017-05, ISPOR 2017, Boston, MA, USA
Value in Health, Vol. 20, No. 5 (May 2017)
Code
PCN6
Topic
Epidemiology & Public Health
Topic Subcategory
Safety & Pharmacoepidemiology
Disease
Oncology