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Medline ® Abstract for Reference 50

of 'Anti-angiogenic and molecularly targeted therapy for advanced or metastatic clear-cell renal cell carcinoma'

50
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Randomized phase III trial of temsirolimus versus sorafenib as second-line therapy after sunitinib in patients with metastatic renal cell carcinoma.
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Hutson TE, Escudier B, Esteban E, Bjarnason GA, Lim HY, Pittman KB, Senico P, Niethammer A, Lu DR, Hariharan S, Motzer RJ
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J Clin Oncol. 2014;32(8):760. Epub 2013 Dec 2.
 
PURPOSE: This international phase III trial (Investigating Torisel As Second-Line Therapy [INTORSECT]) compared the efficacy of temsirolimus (mammalian target of rapamycin inhibitor) and sorafenib (vascular endothelial growth factor receptor [VEGFR]tyrosine kinase inhibitor) as second-line therapy in patients with metastatic renal cell carcinoma (mRCC) after disease progression on sunitinib.
PATIENTS AND METHODS: In total, 512 patients were randomly assigned 1:1 to receive intravenous temsirolimus 25 mg once weekly (n = 259) or oral sorafenib 400 mg twice per day (n = 253), with stratification according to duration of prior sunitinib therapy (≤or>180 days), prognostic risk, histology (clear cell or non-clear cell), and nephrectomy status. The primary end point was progression-free survival (PFS) by independent review committee assessment. Safety, objective response rate (ORR), and overall survival (OS) were secondary end points.
RESULTS: Primary analysis revealed no significant difference between treatment arms for PFS (stratified hazard ratio [HR], 0.87; 95% CI, 0.71 to 1.07; two-sided P = .19) or ORR. Median PFS in the temsirolimus and sorafenib arms were 4.3 and 3.9 months, respectively. There was a significant OS difference in favor of sorafenib (stratified HR, 1.31; 95% CI, 1.05 to 1.63; two-sided P = .01). Median OS in the temsirolimus and sorafenib arms was 12.3 and 16.6 months, respectively. Safety profiles of both agents were consistent with previous studies.
CONCLUSION: In patients with mRCC and progression on sunitinib, second-line temsirolimus did not demonstrate a PFS advantage compared with sorafenib. The longer OS observed with sorafenib suggests sequenced VEGFR inhibition may benefit patients with mRCC.
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Thomas E. Hutson, Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX; Bernard Escudier, Institut Gustave Roussy, Villejuif, France; Emilio Esteban, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain; Georg A. Bjarnason, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada; Ho Yeong Lim, Samsung Medical Center, Seoul, Korea; Kenneth B. Pittman, The Queen Elizabeth Hospital, Woodville South, Adelaide, Australia; Peggy Senico, Pfizer, Collegeville, PA; Andreas Niethammer and Dongrui Ray Lu Pfizer, La Jolla, CA; Subramanian Hariharan, Pfizer; and Robert J. Motzer, Memorial Sloan-Kettering Cancer Center, New York, NY.
PMID