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Efficacy of everolimus in second- and third-line therapy for metastatic renal cell carcinoma: a registry-based
Tomas Buchler1, Zbynek Bortlicek2, Alexandr Poprach3
1Department of Oncology, Thomayer Hospital and Charles University First Faculty of Medicine, Prague, Czech Republic.
Objectives:
The aim of the present study was to describe the efficacy and safety of everolimus in the treatment of metastatic renal cell carcinoma (mRCC) after administration of 1 vs. 2 prior tyrosine kinase inhibitors (TKIs).
Patients And Methods:
A national renal information system database was used as the data source for the retrospective study. There were 483 patients who received everolimus as the second (n = 350) or the third (n = 112) targeted agent following TKIs.
Results:
Median progression-free survival (PFS) from the start of everolimus in the second or the third line of targeted therapy was 6.1 months for both subgroups (P = 0.863). Median total PFS from the start of the first targeted agent to progression on the third targeted agent for patients receiving 3 lines of therapy with TKI-TKI-everolimus (n = 112) and TKI-everolimus-TKI (n = 27) sequences was 28.3 months vs. 31.3 months, respectively (P = 0.16), and there was no significant difference in overall survival. PFS on everolimus was associated with PFS on previous TKIs in patients receiving 1 but not 2 previous TKIs. Only 13% of 352 patients starting targeted therapy for mRCC in 2010 had received 3 sequential targeted agents by the data cutoff in March 2013.
Conclusion:
PFS on everolimus correlated with PFS on TKIs in patients pretreated with 1 but not 2 TKIs. Everolimus can be deferred to the third line without loss of efficacy or increased toxicity. However, only a minority of patients with mRCC starting targeted treatment can be expected to receive third-line therapy.
Insights
Everolimus is effective for metastatic renal cell carcinoma (mRCC) patients, even when used as a third-line treatment after tyrosine kinase inhibitors (TKIs). Progression-free survival on everolimus correlated with prior TKI response in some patients.
Area of Science:
- Oncology
- Pharmacology
Background:
- Metastatic renal cell carcinoma (mRCC) is a complex cancer with limited treatment options.
- Tyrosine kinase inhibitors (TKIs) are a standard first- and second-line therapy for mRCC.
- Everolimus offers a targeted approach for patients progressing on TKIs.
Purpose of the Study:
- To evaluate the efficacy and safety of everolimus in mRCC patients.
- To compare everolimus use after one versus two prior TKIs.
- To assess the impact of prior TKI treatment lines on everolimus outcomes.
Main Methods:
- Retrospective analysis of a national renal information system database.
- Inclusion of 483 patients treated with everolimus as a second or third-line agent post-TKI therapy.
- Comparison of progression-free survival (PFS) and overall survival between treatment groups.
Main Results:
- Median PFS on everolimus was 6.1 months regardless of whether it was second- or third-line therapy.
- No significant difference in overall survival was observed between TKI-TKI-everolimus and TKI-everolimus-TKI sequences.
- PFS on everolimus correlated with PFS on prior TKIs in patients who received one, but not two, prior TKIs.
Conclusions:
- Everolimus demonstrates efficacy and safety when used as a third-line treatment for mRCC.
- Deferring everolimus to the third-line setting does not compromise its effectiveness or increase toxicity.
- A small proportion of mRCC patients are likely to receive third-line targeted therapy.
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