Efficacy of everolimus in second- and third-line therapy for metastatic renal cell carcinoma: A registry-based analysis

• Published in: Urologic oncology 2014-07, Vol.32 (5), p.569-575
• Main Authors: Buchler, Tomas, M.D., Ph.D, Bortlicek, Zbynek, Ph.D, Poprach, Alexandr, M.D., Ph.D, Kubackova, Katerina, M.D, Kiss, Igor, M.D., Ph.D, Zemanova, Milada, M.D., Ph.D, Fiala, Ondrej, M.D, Dusek, Ladislav, Ph.D, Vyzula, Rostislav, M.D., Ph.D, Melichar, Bohuslav, M.D., Ph.D
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Carcinoma, Renal Cell - drug therapy; Databases, Factual; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Drug Therapy - methods; Everolimus; Female; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - therapeutic use; Kidney Neoplasms - drug therapy; Male; Middle Aged; Neoplasm Metastasis; Protein Kinase Inhibitors - therapeutic use; Protein-Tyrosine Kinases - antagonists & inhibitors; Registries; Retrospective Studies; Sirolimus - administration & dosage; Sirolimus - analogs & derivatives; Sirolimus - therapeutic use; Treatment Outcome; Urology
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/j.urolonc.2013.12.007

Abstract 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.