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Sequential targeted therapy after pazopanib therapy in patients with metastatic renal cell cancer: efficacy and
Joaquim Bellmunt1, Francesc Pons2, Abigail Foreshew3
1Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Hospital del Mar, Barcelona, Spain.
Introduction/Background:
Patients with metastatic renal cell carcinoma (mRCC) in whom first-line therapies have failed might derive clinical benefit with sequential targeted agents. Limited data are available on the efficacy and toxicity of subsequent therapies after disease progression during pazopanib therapy.
Patients And Methods:
Patients with mRCC who received subsequent systemic treatment after pazopanib treatment failure were identified across 7 institutions. Pazopanib was given as first-line therapy in 28 patients and after cytokines therapy in 7 patients. Clinical outcome and toxicity analyses of 2 sequential treatment options (anti-vascular endothelial growth factor [VEGF] or mammalian target of rapamycin inhibitor [mTORi]) is presented.
Results:
Subsequent therapy was anti-VEGF in 22 patients and mTORi in 13. One patient who received bevacizumab and temsirolimus combination was excluded. VEGF-targeted therapies included sorafenib (n = 10), sunitinib (n = 3), bevacizumab (n = 2), cediranib (n = 4) and cabozantinib (n = 3). Patients treated with mTORi received everolimus. Median progression-free survival was 5.6 months from the start of subsequent therapy with anti-VEGF and 2.4 months with mTORi (P = .009). Overall survival (OS) was not significantly different (P = .68). Clinical benefit (including partial response and stable disease) on subsequent therapy was observed in 15 patients (64%) and 4 patients (31%) of anti-VEGF- and everolimus-treated patients, respectively (P = .021).
Conclusion:
In this retrospective study, targeting VEGF was an effective strategy after disease progression during pazopanib treatment, although OS was not different among patients treated with VEGF or mTORi.
Insights
Sequential anti-vascular endothelial growth factor (VEGF) therapy shows improved progression-free survival and clinical benefit in metastatic renal cell carcinoma (mRCC) patients after pazopanib failure, compared to mammalian target of rapamycin inhibitors (mTORi).
Area of Science:
- Oncology
- Medical Research
- Pharmacology
Background:
- Metastatic renal cell carcinoma (mRCC) patients often require sequential targeted therapies after initial treatment failure.
- Limited data exist on the efficacy and toxicity of treatments following pazopanib therapy failure in mRCC.
- Pazopanib is a common first-line therapy for mRCC.
Purpose of the Study:
- To evaluate the clinical outcomes and toxicity of sequential targeted agents after pazopanib treatment failure in mRCC patients.
- To compare the efficacy of anti-vascular endothelial growth factor (VEGF) agents versus mammalian target of rapamycin inhibitors (mTORi) as subsequent therapies.
Main Methods:
- Retrospective analysis of mRCC patients (n=35) who received systemic treatment after pazopanib failure across 7 institutions.
- Patients received either anti-VEGF therapy (n=22) or mTORi (everolimus, n=13) as subsequent treatment.
- Clinical outcomes including progression-free survival (PFS), overall survival (OS), and clinical benefit rate were analyzed.
Main Results:
- Median PFS was significantly longer with anti-VEGF therapy (5.6 months) compared to mTORi (2.4 months) (P = .009).
- Clinical benefit rate was higher in the anti-VEGF group (64%) versus the mTORi group (31%) (P = .021).
- Overall survival did not differ significantly between the two treatment groups (P = .68).
Conclusions:
- Anti-VEGF therapy is an effective subsequent treatment strategy for mRCC patients progressing on pazopanib, demonstrating improved PFS and clinical benefit.
- While OS was not significantly different, the improved PFS and clinical benefit suggest anti-VEGF agents are a valuable option.
- Further research may explore optimal sequencing and combinations of targeted agents in mRCC management.
