Abstract
BackgroundTargeted therapies significantly improve clinical outcomes among patients with metastatic renal cell carcinoma (mRCC). Several new agents have been approved for first- and second-line use. However, there is a lack of compelling evidence comparing sequencing strategies, and available comparative data regarding the real-world effectiveness of different therapeutic sequences are limited.Materials and MethodsWe identified mRCC patients who initiated targeted therapy between January 1, 2008 and May 31, 2017 from the National Health Insurance Fund (NHIF) database of Hungary. Overall survival (OS) and duration of first-line treatment (DFT) were obtained for patients receiving sunitinib-everolimus, sunitinib-axitinib, or pazopanib-everolimus treatment sequences. OS of sunitinib-everolimus and sunitinib-axitinib sequences was also determined for patients having better or worse response to sunitinib first-line therapy.ResultsMedian OS was significantly longer among patients treated with sunitinib-axitinib compared to those receiving sunitinib-everolimus. Median DFT was also significantly longer in the sunitinib-axitinib vs. sunitinib-everolimus group. Sunitinib-axitinib was associated with significantly longer median OS compared to sunitinib-everolimus in patients with better response to first-line sunitinib in the pooled sunitinib population. In patients with worse response to sunitinib, sunitinib-axitinib was associated with a trend towards greater OS compared to sunitinib-everolimus, but the difference did not reach statistical significance.ConclusionsIn this nationwide database analysis, mRCC patients treated with the sunitinib-axitinib sequence had significantly longer OS compared to those receiving sunitinib-everolimus therapy. The OS benefits of second-line axitinib were consistent among patients with better response to sunitinib defined by DFT values.
Highlights
Vascular endothelial growth factor (VEGF) and its receptors have a central role in the development and progression of renal1078 Budapest, Hungary 5 Department of Oncotherapy, University of Szeged, Korányi fasor 12, 6720 Szeged, Hungary cell cancer (RCC)
Between January 1 2008 and May 31 2017 318 patients were treated on sunitinib-everolimus, 128 patients on sunitinib-axitinib, and 66 patients on pazopanib-everolimus sequential therapy
Patients with metastatic renal cell carcinoma (mRCC) receiving sunitinib-axitinib had significantly longer median Overall survival (OS) compared to those receiving the sunitinibeverolimus sequence
Summary
Targeting VEGF pathways either by VEGF ligand-binding blockade or by the inhibition of downstream signaling by VEGF receptor (VEGFR) inhibitors has become the mainstay of systemic treatment for metastatic RCC both in first and second line [3]. Eight of the 12 agents ever approved for the treatment of mRCC are anti-VEGFR agents (sorafenib, sunitinib, pazopanib, tivozanib, axitinib, cabozantinib, and lenvatinib), which inhibit tumor angiogenesis to varying degrees. These targeted therapies provide higher efficacy (in terms of PFS or OS) compared to the previous standard-ofcare [4, 5]. OS of sunitinib-everolimus and sunitinib-axitinib sequences was determined for patients having better or worse response to sunitinib first-line therapy
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