Randomized phase III trial of temsirolimus versus sorafenib as second-line therapy after sunitinib in patients with metastatic renal cell carcinoma.

Abstract

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.

• Authors: 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, Robert J Motzer
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 32 Issue 8 Pg. 760-7 (03 10 2014) ISSN: 1527-7755 [Electronic] United States
• PMID: 24297950 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Indoles
• Phenylurea Compounds
• Protein Kinase Inhibitors
• Pyrroles
• Niacinamide
• temsirolimus
• Sorafenib
• MTOR protein, human
• Receptors, Vascular Endothelial Growth Factor
• TOR Serine-Threonine Kinases
• Sunitinib
• Sirolimus

Topics

• Adult
• Aged
• Aged, 80 and over
• Angiogenesis Inhibitors (adverse effects, therapeutic use)
• Carcinoma, Renal Cell (drug therapy, enzymology, mortality, secondary)
• Disease Progression
• Disease-Free Survival
• Female
• Humans
• Indoles (therapeutic use)
• Kaplan-Meier Estimate
• Kidney Neoplasms (drug therapy, enzymology, mortality, pathology)
• Male
• Middle Aged
• Molecular Targeted Therapy
• Niacinamide (adverse effects, analogs & derivatives, therapeutic use)
• Phenylurea Compounds (adverse effects, therapeutic use)
• Protein Kinase Inhibitors (adverse effects, therapeutic use)
• Pyrroles (therapeutic use)
• Receptors, Vascular Endothelial Growth Factor (antagonists & inhibitors, metabolism)
• Sirolimus (adverse effects, analogs & derivatives, therapeutic use)
• Sorafenib
• Sunitinib
• TOR Serine-Threonine Kinases (antagonists & inhibitors, metabolism)
• Time Factors
• Treatment Failure
• Young Adult