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- Title
Efficacy and safety of third-line molecular-targeted therapy in metastatic renal cell carcinoma resistant to first-line vascular endothelial growth factor receptor tyrosine kinase inhibitor and second-line therapy.
- Authors
Ishihara, Hiroki; Takagi, Toshio; Kondo, Tsunenori; Tachibana, Hidekazu; Yoshida, Kazuhiko; Omae, Kenji; Iizuka, Junpei; Kobayashi, Hirohito; Tanabe, Kazunari
- Abstract
Background: The number of studies evaluating the efficacy and safety of third-line molecular-targeted therapy for metastatic renal cell carcinoma (mRCC) is limited.Methods: The data for 48 patients with disease progression after first-line vascular endothelial growth factor receptor tyrosine kinase inhibitor (TKI) and second-line targeted therapy were evaluated. Patients with prior cytokine therapy were excluded. Overall survival (OS) after first- and second-line therapy initiation was compared between patients with and without third-line therapy. In addition, dose-limiting toxicities (DLTs) were evaluated.Results: Twenty-two of 48 patients (45.8%) received third-line therapy, and TKI and mammalian target of rapamycin inhibitor were each administered in 11 patients (50%). Patients with third-line therapy had significantly longer median OS after first-line therapy (26.6 vs. 14.6 months, <italic>p</italic> = 0.0010) and second-line therapy (18.2 vs. 7.4 months, <italic>p</italic> < 0.0001) compared to those without third-line therapy. Multivariate analysis showed that the use of third-line therapy following second-line therapy was an independent prognosticator for longer OS (hazard ratio 0.29, 95% confidence interval 0.14-0.58, <italic>p</italic> = 0.0005). The median progression-free survival and OS after third-line therapy was 2.76 and 8.71 months, respectively. Although a high frequency of DLTs was observed (<italic>n</italic> = 10, 45.5%), the frequencies were similar among the sequential therapies.Conclusions: Third-line therapy has a beneficial therapeutic effect in patients with mRCC that is resistant to previous therapies. However, there is a need to evaluate in detail the high frequency of adverse events, including DLTs.
- Subjects
CANCER treatment; RENAL cell carcinoma; PROTEIN-tyrosine kinase inhibitors; MOLECULAR oncology; VASCULAR endothelial growth factor receptors; DRUG efficacy; MEDICATION safety; METASTASIS
- Publication
International Journal of Clinical Oncology, 2018, Vol 23, Issue 3, p559
- ISSN
1341-9625
- Publication type
Article
- DOI
10.1007/s10147-018-1241-3