• Thomas E Hutson, Bernard Escudier, Emilio Esteban, Georg A Bjarnason, Ho Yeong Lim, Kenneth B Pittman, Peggy Senico, Andreas Niethammer, Dongrui Ray Lu, Subramanian Hariharan, and Robert J Motzer.
• 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.
• J. Clin. Oncol. 2014 Mar 10; 32 (8): 760-7.

PurposeThis 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 MethodsIn 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.ResultsPrimary 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.ConclusionIn 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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