Temsirolimus versus Pazopanib (TemPa) in Patients with Advanced Clear-cell Renal Cell Carcinoma and Poor-risk Features: A Randomized Phase II Trial
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Published on: February 8, 2020
Nizar M Tannir1, Pavlos Msaouel1, Jeremy A Ross1
1Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Background:
Temsirolimus has level 1 evidence for initial treatment of poor-risk patients with advanced renal cell carcinoma (mRCC), but its efficacy has not been directly compared with an antiangiogenic tyrosine kinase inhibitor (vascular endothelial growth factor receptor tyrosine kinase inhibitor [VEGFR TKi]) in this setting.
Objective:
To evaluate temsirolimus versus pazopanib as first-line therapy in patients with mRCC, predominant clear-cell features, and clinical characteristics of a poor prognosis.
Design, Setting, And Participants:
A randomized (1:1) phase II trial in 69 treatment-naïve mRCC patients and with three or more predictors of short survival for temsirolimus was conducted during 2012-2017 in a single academic cancer center. Crossover to the alternative treatment upon discontinuation of the first-line agent was permitted.
Intervention:
Mechanistic target of rapamycin inhibitor temsirolimus and VEGFR TKi pazopanib.
Outcome Measurements And Statistical Analysis:
The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), safety, and patient-reported outcomes (PROs). Radiographic response was assessed by blinded radiologists. Efficacy outcomes were adjusted by prior nephrectomy status, prior interleukin-2 treatment, and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score.
Results And Limitations:
Thirty-five patients received temsirolimus and 34 received pazopanib upfront; 72% overall had poor risk by IMDC. Median PFS in the first line was 2.7mo with temsirolimus and 5.2mo with pazopanib (adjusted hazard ratio [HR] 1.36, 95% confidence interval [CI] 0.84-2.22; p=0.210). Median OS was 7.1mo with temsirolimus and 11.9mo with pazopanib (adjusted HR 1.16, 95% CI 0.70-1.93; p=0.558), and ORRs were 5.9% and 21.2%, respectively (adjusted odds ratio 5.2, 95% CI 0.9-29.3; p=0.062). PRO measures favored pazopanib. Five patients discontinued first-line therapy due to adverse events.
Conclusions:
Temsirolimus and pazopanib had modest activity in patients with poor-risk clear-cell mRCC, and therefore their use should be discouraged in this setting.
Patient Summary:
We evaluated outcomes of advanced renal cell carcinoma patients presenting with aggressive features when treated with temsirolimus or pazopanib as first-line therapy. Survival was <1yr for most, suggesting that more efficacious alternative treatments should be favored for these patients.
Insights
Temsirolimus and pazopanib showed limited effectiveness as initial treatments for advanced clear-cell renal cell carcinoma with poor prognosis. These therapies are not recommended for this patient group, highlighting the need for more effective alternatives.
Area of Science:
- Oncology
- Medical research
Background:
- Temsirolimus is indicated for advanced renal cell carcinoma (mRCC) in poor-risk patients, but direct comparisons with antiangiogenic tyrosine kinase inhibitors (VEGFR TKIs) are lacking.
- Clear-cell mRCC with poor prognostic factors presents a challenge for first-line treatment selection.
Purpose of the Study:
- To compare the efficacy of temsirolimus versus pazopanib as first-line therapy for patients with advanced clear-cell renal cell carcinoma and poor prognostic features.
- To assess progression-free survival (PFS), overall survival (OS), objective response rate (ORR), safety, and patient-reported outcomes (PROs).
Main Methods:
- A randomized phase II trial involving 69 treatment-naïve mRCC patients with at least three short-survival predictors.
- Patients received either temsirolimus or pazopanib as first-line therapy, with crossover permitted upon discontinuation.
- Efficacy outcomes were adjusted for prior nephrectomy, prior interleukin-2 treatment, and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) scores.
Main Results:
- Median PFS was 2.7 months for temsirolimus and 5.2 months for pazopanib (adjusted HR 1.36, p=0.210).
- Median OS was 7.1 months for temsirolimus and 11.9 months for pazopanib (adjusted HR 1.16, p=0.558).
- Objective response rates were 5.9% for temsirolimus and 21.2% for pazopanib (adjusted OR 5.2, p=0.062); PROs favored pazopanib.
Conclusions:
- Both temsirolimus and pazopanib demonstrated modest activity in poor-risk clear-cell mRCC patients.
- Their use as first-line therapy in this setting is discouraged due to limited efficacy.
- More effective treatment options should be prioritized for patients with advanced renal cell carcinoma and aggressive features.
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