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Modeling Spontaneous Metastatic Renal Cell Carcinoma (mRCC) in Mice Following Nephrectomy
Published on: April 29, 2014
Primary anti-vascular endothelial growth factor (VEGF)-refractory metastatic renal cell carcinoma: clinical
D Y Heng1, M J Mackenzie, U N Vaishampayan
1Department of Medical Oncology, University of Calgary, Calgary, Canada. daniel.heng@albertahealthservices.ca
Background:
A subset of patients treated with initial anti-vascular endothelial growth factor (VEGF) therapy exhibit progressive disease (PD) as the best response per RECIST criteria.
Methods:
Data from patients with metastatic renal cell carcinoma (mRCC) treated with anti-VEGF therapy were collected through the International mRCC Database Consortium from 12 centers.
Results:
One thousand and fifty-six assessable patients received initial VEGF inhibitors and 272 (26%) of these patients had PD as best response. Initial treatment included sunitinib (n = 203), sorafenib (n = 51), or bevacizumab (n = 18). Six percent of patients were at favorable risk, 55% at intermediate risk, and 39% at poor risk. On multivariable analysis, predictors of PD were Karnofsky performance status < 80% [odds ratio (OR) = 2.3, P < 0.0001], diagnosis to treatment < 1 year (OR = 2.1, P < 0.0001), neutrophilia (OR = 1.9, P = 0.0021), thrombocytosis (OR = 1.7, P = 0.0068), and anemia (OR = 1.6, P = 0.0058). Median progression-free survival (PFS) in patients with PD versus without PD was 2.4 versus 11 months (P < 0.0001) and overall survival (OS) was 6.8 versus 29 months (P < 0.0001), respectively. One hundred and eight (40%) VEGF-refractory patients proceeded to receive further systemic therapies. Response rate, PFS, and OS for subsequent therapy were 9%, 2.5 months, and 7.4 months, respectively, with no statistical differences between patients who received VEGF versus mammalian target of rapamycin (mTOR) inhibitors.
Conclusions:
Primary anti-VEGF-refractory mRCC patients have a dismal prognosis. Second-line anti-mTOR and anti-VEGF agents produce similar outcomes.
Insights
A subset of metastatic renal cell carcinoma (mRCC) patients exhibit progressive disease (PD) despite initial anti-vascular endothelial growth factor (VEGF) therapy. These VEGF-refractory patients have a poor prognosis, with similar outcomes for subsequent anti-mammalian target of rapamycin (mTOR) or anti-VEGF treatments.
Area of Science:
- Oncology
- Medical Research
- Clinical Trials
Background:
- A portion of patients with metastatic renal cell carcinoma (mRCC) do not respond to initial anti-vascular endothelial growth factor (VEGF) therapy, showing progressive disease (PD).
- Understanding predictors and outcomes for this refractory group is crucial for optimizing mRCC treatment strategies.
Purpose of the Study:
- To identify predictors of primary progressive disease (PD) in metastatic renal cell carcinoma (mRCC) patients treated with anti-vascular endothelial growth factor (VEGF) therapy.
- To evaluate the prognosis and outcomes of subsequent therapies in VEGF-refractory mRCC patients.
Main Methods:
- Data from 1056 metastatic renal cell carcinoma (mRCC) patients receiving initial anti-VEGF therapy were analyzed from the International mRCC Database Consortium.
- Multivariable analysis identified predictors of PD, and progression-free survival (PFS) and overall survival (OS) were compared between PD and non-PD groups.
- Outcomes of subsequent therapies (VEGF vs. mammalian target of rapamycin (mTOR) inhibitors) were assessed in VEGF-refractory patients.
Main Results:
- 26% of patients experienced PD as their best response to initial anti-VEGF therapy. Predictors of PD included poor performance status, short diagnosis-to-treatment interval, neutrophilia, thrombocytosis, and anemia.
- Patients with PD had significantly shorter median PFS (2.4 vs. 11 months) and OS (6.8 vs. 29 months) compared to non-PD patients.
- In VEGF-refractory patients, subsequent therapies showed a response rate of 9%, median PFS of 2.5 months, and median OS of 7.4 months, with no significant difference between anti-VEGF and anti-mTOR agents.
Conclusions:
- Metastatic renal cell carcinoma (mRCC) patients refractory to primary anti-VEGF therapy face a dismal prognosis.
- Second-line treatment with either anti-mammalian target of rapamycin (mTOR) or further anti-VEGF agents yields similar, limited outcomes.
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