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First-line therapy for treatment-naive patients with advanced/metastatic renal cell carcinoma: a systematic review of
Shweta Takyar1, Jose Diaz, Manu Sehgal
1aPAREXEL International, Chandigarh, India bNovartis Pharma AG, Basel, Switzerland cAstraZeneca, Cambridge dDepartment of Oncology, University of Surrey, Surrey, UK.
Abstract:
In the recent years, a number of targeted therapies have been approved for first-line treatment of patients with metastatic renal cell carcinoma. A systematic review was conducted to assess the clinical efficacy, safety and effect of all first-line treatments evaluated to date on health-related quality of life (HRQoL). A systematic search of Embase, Cochrane and MEDLINE databases was performed to identify randomized controlled trials (1980-2015) evaluating any targeted therapy/immunotherapy against placebo or any other targeted intervention/immunotherapy in treatment-naive patients with metastatic renal cell carcinoma. Conference proceedings from major cancer congresses (2007-2015) were handsearched. Sixteen randomized controlled trials were identified, mostly phase III. Overall, targeted therapies were associated with either improved [sunitinib, bevacizumab+interferon α (IFNα) and temsirolimus] or comparable (sorafenib) progression-free survival (PFS) versus IFNα monotherapy. Sunitinib demonstrated comparable PFS and overall survival to pazopanib, comparable PFS to sorafenib and shorter PFS compared with bevacizumab+IFNα (although no conclusions were made with regard to superiority/inferiority). Compared with sorafenib, tivozanib demonstrated a significantly longer PFS, and both tivozanib and axitinib demonstrated higher response rates. Nintedanib demonstrated comparable PFS and overall survival to sunitinib in a phase II trial. Temsirolimus, sunitinib and sorafenib treatment led to better HRQoL versus IFNα; pazopanib was associated with better HRQoL versus sunitinib. No direct meta-analyses or indirect treatment comparison analysis were undertaken because of noncomparability of the trials. In general, targeted therapies demonstrated favourable clinical efficacy and improved HRQoL compared with IFNα monotherapy. The newer therapies, tivozanib and axitinib (but not nintedanib), appeared to exhibit greater clinical benefit (response rate) than older tyrosine kinase inhibitors.
Insights
Targeted therapies improve progression-free survival and quality of life for metastatic renal cell carcinoma patients compared to interferon alfa. Newer agents like tivozanib and axitinib show enhanced response rates.
Area of Science:
- Oncology
- Clinical Pharmacology
Background:
- Metastatic renal cell carcinoma (mRCC) treatment has evolved with targeted therapies.
- Assessing first-line treatment efficacy and impact on quality of life is crucial.
Purpose of the Study:
- To systematically review first-line targeted therapies for mRCC.
- To evaluate clinical efficacy, safety, and health-related quality of life (HRQoL).
Main Methods:
- Systematic search of Embase, Cochrane, and MEDLINE databases (1980-2015).
- Included randomized controlled trials (RCTs) of targeted therapies/immunotherapies vs. placebo or other interventions in treatment-naive mRCC patients.
- Handsearched major cancer congress proceedings (2007-2015).
Main Results:
- Sixteen RCTs identified; most were Phase III.
- Targeted therapies showed improved or comparable progression-free survival (PFS) versus interferon alfa (IFNα).
- Sunitinib, temsirolimus, and sorafenib improved HRQoL versus IFNα; pazopanib improved HRQoL versus sunitinib.
Conclusions:
- First-line targeted therapies demonstrate favorable clinical efficacy and improved HRQoL compared to IFNα monotherapy.
- Newer agents like tivozanib and axitinib show greater clinical benefit (response rate) than older tyrosine kinase inhibitors.
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