OBJECTIVE: The optimal sequencing of targeted therapies for metastatic renal cell carcinoma (mRCC) is unknown.
Observational studies with a variety of designs have reported differing results. The objective of this study is to systematically summarize and interpret the published real-world evidence comparing sequential treatment for mRCC.
METHODS: A search was conducted in Medline and Embase (2009-2013), and conference proceedings from American Society of Clinical Oncology (ASCO), ASCO Genitourinary Cancers Symposium (ASCO-GU), and European Society for Medical Oncology (ESMO) (2011-2013). We systematically reviewed observational studies comparing second-line mRCC treatment with mammalian target of rapamycin inhibitors (mTORi) versus vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI). Studies were evaluated for 1) use of a retrospective cohort design after initiation of second-line therapy, 2) adjustment for patient characteristics, and 3) use of data from multiple centers. Meta-analyses were conducted for comparisons of overall survival (OS) and progression-free survival (PFS).
RESULTS: Ten studies reported OS and exhibited significant heterogeneity in estimated second-line treatment effects (I2 = 68%; P = 0.001). Four of these were adjusted, multicenter, retrospective cohort studies, and these showed no evidence of heterogeneity (I2 = 0%; P = 0.61) and a significant association between second-line mTORi (>75% everolimus) and longer OS compared to VEGF TKI (>60% sorafenib) (HR = 0.82, 95% CI: 0.68 to 0.98) in a meta-analysis. Seven studies comparing PFS showed significant heterogeneity overall and among the adjusted, multicenter, retrospective cohort studies. Real-world observational data for axitinib outcomes was limited at the time of this study.
CONCLUSIONS: Real-world studies employed different designs and reported heterogeneous results comparing the effectiveness of second-line mTORi and VEGF TKI in the treatment of mRCC. Within the subset of adjusted, multicenter observational studies, second-line use of mTORi was associated with significantly prolonged survival compared with second-line use of VEGF TKI.
Written by:
Heng DY, Signorovitch J, Swallow E, Li N, Zhong Y, Qin P, Zhuo DY, Wang X, Park J, Stergiopoulos S, Kollmannsberger C. Are you the author?
Department of Medical Oncology, Tom Baker Cancer Center, Alberta Health Services Cancer Care, University of Calgary, Calgary, Canada; Analysis Group, Inc., Boston, Massacusetts, United States of America; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States of America; Department of Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Reference: PLoS One. 2014 Dec 10;9(12):e114264.
doi: 10.1371/journal.pone.0114264
PubMed Abstract
PMID: 25493562