Temsirolimus versus Pazopanib (TemPa) in Patients with Advanced Clear-cell Renal Cell Carcinoma and Poor-risk Features: A Randomized Phase II Trial.

ABSTRACT:

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.

SUBMITTER: Tannir NM 

PROVIDER: S-EPMC6938577 | biostudies-literature |

REPOSITORIES: biostudies-literature