Efficacy and safety of sequential use of everolimus in Japanese patients with advanced renal cell carcinoma after failure of first-line treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitor: a multicenter phase II clinical trial.
OBJECTIVE
Many studies have shown the efficacy of everolimus after pretreatment with vascular endothelial growth factor receptor-tyrosine kinase inhibitors. We investigated the efficacy and safety of everolimus as a second-line treatment after the failure of vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy in Japanese patients with advanced renal cell carcinoma.


METHODS
This was an open-label, multicenter, phase II trial conducted in Japan through the central registration system. A total of 57  patients were enrolled. Patients were administered 10 mg of everolimus q.d. orally. The primary efficacy endpoint was progression-free survival achieved by administration of everolimus.


RESULTS
The median progression-free survival of patients administered everolimus was 5.03 months (95% confidence interval: 3.70-6.20). The median overall survival was not reached. The objective response rate was 9.4% (95% confidence interval: 3.1-20.7). The progression-free survival in the group of <100% relative dose intensity was 6.70 months (95% confidence interval: 4.13-11.60), and that in the group of 100% relative dose intensity was 3.77 months (hazard ratio: 2.79, 95% confidence interval: 2.77-5.63). The commonly observed adverse events and laboratory abnormalities were stomatitis (49.1%), hypertriglyceridemia (26.4%), interstitial lung disease (26.4%), anemia (22.6%) and hypercholesterolemia (22.6%).


CONCLUSIONS
The median progression-free survival was almost similar to that recorded in the RECORD-1 study, whereas prolongation of overall survival was observed in the present study compared with the RECORD-1 study. The treatment outcomes of first-line vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy and second-line everolimus treatment in Japanese patients were successfully established in the present study.
Saitama Medical University International Medical Center, Hidaka, Japan.
Masafumi
M
Oyama
Hamamatsu University School of Medicine, Hamamatsu, Japan.
Takayuki
T
Sugiyama
Kindai University Faculty of Medicine, Osaka-sayama, Japan.
Masahiro
M
Nozawa
Nara Medical University, Kashihara, Japan.
Kiyohide
K
Fujimoto
Kanagawa Cancer Center, Yokohama, Japan.
Takeshi
T
Kishida
Nippon Medical School, Tokyo, Japan.
Go
G
Kimura
Saga-Ken Medical Centre Koseikan, Saga, Japan.
Noriaki
N
Tokuda
Okayama University, Okayama, Japan.
Shiro
S
Hinotsu
Ritsumeikan University, Kusatsu, Japan.
Kojiro
K
Shimozuma
Interfaculty Initiative in Information Studies/Graduate School of Interdisciplinary Information Studies, The University of Tokyo, Tokyo, Japan.
Hideyuki
H
Akaza
Hamamatsu University School of Medicine, Hamamatsu, Japan.
Seiichiro
S
Ozono
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D044466:Asian People; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D003710:Demography; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D000068338:Everolimus / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017211:Treatment Failure; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000068338:Everolimus; D011505:Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor
everolimus, renal cell carcinoma, mTOR, Japan