A pooled analysis of sequential therapies with sorafenib and sunitinib in metastatic renal cell carcinoma.
OBJECTIVE
To evaluate the optimal sequence for the receptor tyrosine kinase inhibitors (rTKIs) sorafenib and sunitinib in metastatic renal cell cancer.


METHODS
We performed a retrospective analysis of patients who had received sequential therapy with both rTKIs and integrated these results into a pooled analysis of available data from other publications. Differences in median progression-free survival (PFS) for first- (PFS1) and second-line treatment (PFS2), and for the combined PFS (PFS1 plus PFS2) were examined using weighted linear regression.


RESULTS
In the pooled analysis encompassing 853 patients, the median combined PFS for first-line sunitinib and 2nd-line sorafenib (SuSo) was 12.1 months compared with 15.4 months for the reverse sequence (SoSu; 95% CI for difference 1.45-5.12, p = 0.0013). Regarding first-line treatment, no significant difference in PFS1 was noted regardless of which drug was initially used (0.62 months average increase on sorafenib, 95% CI for difference -1.01 to 2.26, p = 0.43). In second-line treatment, sunitinib showed a significantly longer PFS2 than sorafenib (average increase 2.66 months, 95% CI 1.02-4.3, p = 0.003).


CONCLUSIONS
The SoSu sequence translates into a longer combined PFS compared to the SuSo sequence. Predominantly the superiority of sunitinib regarding PFS2 contributed to the longer combined PFS in sequential use.
Department of Medical Oncology, University Hospital Zurich, Zurich, Switzerland. frank.stenner@usz.ch
Frank
F
Stenner
Rahel
R
Chastonay
Heike
H
Liewen
Sarah R
SR
Haile
Richard
R
Cathomas
Christian
C
Rothermundt
Raffaele D
RD
Siciliano
Susanna
S
Stoll
Alexander
A
Knuth
Tomas
T
Buchler
Camillo
C
Porta
Christoph
C
Renner
Panagiotis
P
Samaras
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001557:Benzenesulfonates / Q000008:administration & dosage; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D012189:Retrospective Studies; D000077157:Sorafenib; D000077210:Sunitinib; D016896:Treatment Outcome
D001557:Benzenesulfonates; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D000077210:Sunitinib