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
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The number of studies evaluating the efficacy and safety of third-line molecular-targeted therapy for metastatic renal cell carcinoma (mRCC) is limited.
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.
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, p = 0.0010) and second-line therapy (18.2 vs. 7.4 months, p < 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, p = 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 (n = 10, 45.5%), the frequencies were similar among the sequential therapies.
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.
KeywordsRenal cell carcinoma Targeted therapy Third-line therapy Tyrosine kinase inhibitor mTORi Metastasis
The authors thank Editage for English language editing and Nobuko Hata for secretarial support.
Compliance with ethical standards
Conflict of interest
Tsunenori Kondo received honoraria from Pfizer, Bayer, and Novartis. None of the other authors have any conflicts of interest to declare.
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