Everolimus in metastatic renal cell carcinoma: Subgroup analysis of patients with 1 or 2 previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapies enrolled in the phase III RECORD-1 study.
BACKGROUND
In the phase III RECORD-1 trial (ClinicalTrials.gov: NCT00410124), patients with metastatic renal cell carcinoma (mRCC) who progressed on previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFr-TKI) therapy were randomised 2:1 to everolimus 10mg once daily (n=277) or placebo (n=139). Median progression-free survival (PFS) was 4.9months with everolimus and 1.9months with placebo (hazard ratio [HR], 0.33; P<.001). This preplanned, prospective sub-analysis evaluated PFS benefit of everolimus versus placebo in patients who had previously received 1 or 2 VEGFr-TKIs.


METHODS
Median PFS was estimated using the Kaplan-Meier method, and Cox proportional hazards model was used to analyse differences in PFS.


RESULTS
All patients (100%) received ⩾1 previous VEGFr-TKI; 26% of patients received 2 previous VEGFr-TKIs. Among patients who received 1 previous VEGFr-TKI, median PFS was 5.4months with everolimus and 1.9months with placebo (HR, 0.32; 95%confidence interval [CI], 0.24-0.43; P<.001). Among patients who received 2 previous VEGFr-TKIs, median PFS was 4.0months with everolimus and 1.8months with placebo (HR, 0.32; 95%CI, 0.19-0.54; P<.001). The everolimus safety profile was similar for both groups.


CONCLUSIONS
Everolimus was associated with prolonged PFS relative to placebo in patients who received 1 or 2 previous VEGFr-TKIs. Patients who received only 1 previous VEGFr-TKI had apparently longer PFS with everolimus in reference to those who received 2 previous VEGFr-TKIs. These results support the use of everolimus as the standard of care in patients who fail initial VEGFr-TKI therapy.
START Madrid, Centro Integral Oncológico Clara Campal, Hospital Madrid Norte Sanchinarro, Madrid, Spain. emiliano.calvo@start.stoh.com
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E
Calvo
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Escudier
R J
RJ
Motzer
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Oudard
T E
TE
Hutson
C
C
Porta
S
S
Bracarda
V
V
Grünwald
J A
JA
Thompson
A
A
Ravaud
D
D
Kim
A
A
Panneerselvam
O
O
Anak
R A
RA
Figlin
D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D018572:Disease-Free Survival; D004311:Double-Blind Method; D000068338:Everolimus; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D016016:Proportional Hazards Models; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors; D000068338:Everolimus; D040262:Receptors, Vascular Endothelial Growth Factor; D020123:Sirolimus