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Metastatic non-clear cell renal cell carcinoma: an evidence based review of current treatment strategies.

Sankin A, Hakimi AA, Hsieh JJ, Molina AM - Front Oncol (2015)

Bottom Line: Much progress has been made in the treatment of metastatic renal cell carcinoma (RCC) over the last decade, with the development of agents that block the vascular endothelial growth factor (VEGF) pathway or the mammalian target of rapamycin (mTOR) pathway.The incorporation of these agents into treatment algorithms has been the result of carefully conducted clinical trials leading to Food and Drug Administration (FDA) approval and subsequent adoption as the current standard of care.This review is a pathway based approach that highlights the current systemic treatment strategies for metastatic nccRCC.

View Article: PubMed Central - PubMed

Affiliation: Memorial Sloan-Kettering Cancer Center , New York, NY , USA.

ABSTRACT
Much progress has been made in the treatment of metastatic renal cell carcinoma (RCC) over the last decade, with the development of agents that block the vascular endothelial growth factor (VEGF) pathway or the mammalian target of rapamycin (mTOR) pathway. The incorporation of these agents into treatment algorithms has been the result of carefully conducted clinical trials leading to Food and Drug Administration (FDA) approval and subsequent adoption as the current standard of care. These trials, however, were dominated by patients with clear cell renal cell carcinoma (ccRCC), and little data are currently available on the treatment of non-clear cell renal cell carcinoma (nccRCC). nccRCC encompasses a biologically heterogeneous group of kidney tumors that portend very diverse prognoses and responses to therapy. This review is a pathway based approach that highlights the current systemic treatment strategies for metastatic nccRCC.

No MeSH data available.


Related in: MedlinePlus

Hazard ratios (indicated by circles) with 95% confidence intervals (indicated by horizontal lines) are shown for subgroups of patients receiving interferon-α or temsirolimus.
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Figure 2: Hazard ratios (indicated by circles) with 95% confidence intervals (indicated by horizontal lines) are shown for subgroups of patients receiving interferon-α or temsirolimus.

Mentions: Temsirolimus, an mTOR inhibitor, was approved for treatment of advanced RCC after the ARCC trial. This large, multi-institutional phase 3 trial studied the effects of temsirolimus as first line therapy for poor-prognosis advanced RCC (32). A total of 626 patients were randomly assigned to temsirolimus, interferon-α, or combination therapy. Patients randomized to the temsirolimus group had a longer overall survival compared to the interferon and combination group (10.9 vs 7.3 and 8.4 months, respectively). While this study included patients with all histologies of RCC, the data suggested a more pronounced survival advantage in patients with non-clear cell histology, which prompted a subgroup analysis (Figure 2). In this analysis, they identified 73 patients with nccRCC (37 randomized to temsirolimus arm and 36 to the interferon-α arm) (33). Within this cohort, they observed an improved clinical benefit (defined as complete or partial response or stable disease ≥24 weeks) of temsirolimus over interferon alpha (35.1 vs 8.3%, respectively). They also observed a greater degree of improvement among the non-clear cell subgroup compared to the clear cell patients, but this finding was not statistically significant. The authors speculated that the clinical improvement observed with temsirolimus on non-clear cell tumors may be due to the critical role of angiogenesis in all RCC histologies as well as the close relationship between mTOR and c-Met pathways. Temsirolimus is the only agent with a NCCN category 1 recommendation (in poor prognosis patients according to MSKCC criteria) for metastatic non-clear cell disease (30). It has a category 2A recommendation for all other prognostic risk groups.


Metastatic non-clear cell renal cell carcinoma: an evidence based review of current treatment strategies.

Sankin A, Hakimi AA, Hsieh JJ, Molina AM - Front Oncol (2015)

Hazard ratios (indicated by circles) with 95% confidence intervals (indicated by horizontal lines) are shown for subgroups of patients receiving interferon-α or temsirolimus.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4389537&req=5

Figure 2: Hazard ratios (indicated by circles) with 95% confidence intervals (indicated by horizontal lines) are shown for subgroups of patients receiving interferon-α or temsirolimus.
Mentions: Temsirolimus, an mTOR inhibitor, was approved for treatment of advanced RCC after the ARCC trial. This large, multi-institutional phase 3 trial studied the effects of temsirolimus as first line therapy for poor-prognosis advanced RCC (32). A total of 626 patients were randomly assigned to temsirolimus, interferon-α, or combination therapy. Patients randomized to the temsirolimus group had a longer overall survival compared to the interferon and combination group (10.9 vs 7.3 and 8.4 months, respectively). While this study included patients with all histologies of RCC, the data suggested a more pronounced survival advantage in patients with non-clear cell histology, which prompted a subgroup analysis (Figure 2). In this analysis, they identified 73 patients with nccRCC (37 randomized to temsirolimus arm and 36 to the interferon-α arm) (33). Within this cohort, they observed an improved clinical benefit (defined as complete or partial response or stable disease ≥24 weeks) of temsirolimus over interferon alpha (35.1 vs 8.3%, respectively). They also observed a greater degree of improvement among the non-clear cell subgroup compared to the clear cell patients, but this finding was not statistically significant. The authors speculated that the clinical improvement observed with temsirolimus on non-clear cell tumors may be due to the critical role of angiogenesis in all RCC histologies as well as the close relationship between mTOR and c-Met pathways. Temsirolimus is the only agent with a NCCN category 1 recommendation (in poor prognosis patients according to MSKCC criteria) for metastatic non-clear cell disease (30). It has a category 2A recommendation for all other prognostic risk groups.

Bottom Line: Much progress has been made in the treatment of metastatic renal cell carcinoma (RCC) over the last decade, with the development of agents that block the vascular endothelial growth factor (VEGF) pathway or the mammalian target of rapamycin (mTOR) pathway.The incorporation of these agents into treatment algorithms has been the result of carefully conducted clinical trials leading to Food and Drug Administration (FDA) approval and subsequent adoption as the current standard of care.This review is a pathway based approach that highlights the current systemic treatment strategies for metastatic nccRCC.

View Article: PubMed Central - PubMed

Affiliation: Memorial Sloan-Kettering Cancer Center , New York, NY , USA.

ABSTRACT
Much progress has been made in the treatment of metastatic renal cell carcinoma (RCC) over the last decade, with the development of agents that block the vascular endothelial growth factor (VEGF) pathway or the mammalian target of rapamycin (mTOR) pathway. The incorporation of these agents into treatment algorithms has been the result of carefully conducted clinical trials leading to Food and Drug Administration (FDA) approval and subsequent adoption as the current standard of care. These trials, however, were dominated by patients with clear cell renal cell carcinoma (ccRCC), and little data are currently available on the treatment of non-clear cell renal cell carcinoma (nccRCC). nccRCC encompasses a biologically heterogeneous group of kidney tumors that portend very diverse prognoses and responses to therapy. This review is a pathway based approach that highlights the current systemic treatment strategies for metastatic nccRCC.

No MeSH data available.


Related in: MedlinePlus