Small molecule targeted therapies for the second-line treatment for metastatic renal cell carcinoma: a systematic review and indirect comparison of safety and efficacy

  title={Small molecule targeted therapies for the second-line treatment for metastatic renal cell carcinoma: a systematic review and indirect comparison of safety and efficacy},
  author={George Dranitsaris and Susanne Schmitz and Reuben James Broom},
  journal={Journal of Cancer Research and Clinical Oncology},
AbstractBackground Patients with metastatic renal cell carcinoma (mRCC) and a good performance status typically receive an anti-vascular endothelial growth factor receptor (VEGFR) TKI (sunitinib or pazopanib) as initial therapy. Upon disease progression or intolerance, there are four orally administered agents approved in the second-line setting (including cytokine-refractory). However, head-to-head comparative trial data are limited. In this study, an indirect statistical comparison of safety… 
Targeted therapies for previously treated advanced or metastatic renal cell carcinoma: systematic review and network meta-analysis
Lenvatinib with everolimus, cabozantinib and nivolumab are effective in prolonging the survival for people with amRCC subsequent to VEGF-targeted treatment, but there is considerable uncertainty about how they compare to each other and how much better they are than axit inib and sorafenib.
Axitinib in the treatment of renal cell carcinoma: design, development, and place in therapy
The field of RCC treatment is rapidly changing with novel TKIs as cabozantinib or the emergence of check point inhibitors as nivolumab and the place of axitinib in therapy is therefore challenged.
Axitinib for the treatment of advanced renal cell carcinoma
Axitinib is generally well-tolerated and provides definitive clinical benefits in patients with advanced or metastatic RCC as second-line therapy, however, as with other tyrosine kinase inhibitors of the same class, axitinib does not prolong overall survival; therefore, selection of second- line tyrosINE kinase inhibitor therapy, including axit inib, must be carefully considered to maximize outcomes for each patient.
Everolimus in the management of metastatic renal cell carcinoma: an evidence-based review of its place in therapy
Everolimus still represents a current standard of treatment for RCC progressive to previous treatment lines with VEGFR-TKI, and the main downstream effectors of mTOR cascade, S6RP and its phosphorylated form, could be good predictive biomarkers of response to everolimus.
Lifetime cost of everolimus vs axitinib in patients with advanced renal cell carcinoma who failed prior sunitinib therapy in the US
It is suggested that everolimus likely leads to lower lifetime costs than axitinib for sunit inib-refractory advanced RCC patients in the US.
Real-world dosing and drug costs with everolimus or axitinib as second targeted therapies for advanced renal cell carcinoma: a retrospective chart review in the US
Patients with aRCC receiving axitinib as second targeted therapy were more likely to initiate at a higher than label-recommended dose and were morelikely to dose escalate than patients receiving everolimus, and drug costs were significantly higher—by 17% per month of PFS—with axit inib than with everolitus.
The need for new algorithms of treatment sequencing in clear-cell metastatic renal cell carcinoma
All systemic therapeutic options currently available are reviewed, the evidence behind the current options available for mRCC patient treatment is described, and personal cues to support clinical decisions are provided.


Metastatic renal cell cancer treatments: An indirect comparison meta-analysis
New interventions for mRCC offer a favourable PFS compared to interferon-α and placebo, and all interventions offer advantages for PFS.
Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial.
  • C. Sternberg, I. Davis, R. Hawkins
  • Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2010
Pazopanib demonstrated significant improvement in PFS and tumor response compared with placebo in treatment-naive and cytokine-pretreated patients with advanced and/or metastatic RCC.
Sorafenib for treatment of renal cell carcinoma: Final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial.
  • B. Escudier, T. Eisen, R. Bukowski
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2009
Although an OS benefit was not seen on a primary intent-to-treat analysis, results of a secondary OS analysis censoring placebo patients demonstrated a survival advantage for those receiving sorafenib, suggesting an important cross-over effect.
Second-line treatments for the management of advanced renal cell carcinoma: systematic review and meta-analysis
It is suggested that axitinib will be an important treatment option to extend PFS in the management of advanced RCC in the second-line setting and ongoing research will define the optimal treatment algorithm leading to a patient-focused treatment strategy.