TY - JOUR
T1 - Meta-analysis of stomatitis in clinical studies of everolimus
T2 - Incidence and relationship with efficacy
AU - Rugo, Hope S.
AU - Hortobagyi, G. N.
AU - Yao, J.
AU - Pavel, M.
AU - Ravaud, A.
AU - Franz, D.
AU - Ringeisen, F.
AU - Gallo, J.
AU - Rouyrre, N.
AU - Anak, O.
AU - Motzer, R.
N1 - Publisher Copyright:
© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - Background: Everolimus, an oral mammalian target of rapamycin (mTOR) inhibitor, is used to treat solid tumors and tuberous sclerosis complex (TSC). Stomatitis, an inflammation of the mucous membranes of the mouth, is a common adverse event associated with mTOR inhibitors, including everolimus. We conducted a meta-analysis of data from seven randomized, double-blind phase 3 clinical trials of everolimus to determine the clinical impact of stomatitis on efficacy and safety. Patients and methods: Data were pooled from the safety sets of solid tumor [breast cancer (BOLERO-2 and BOLERO-3), renal cell carcinoma (RECORD-1), carcinoid tumors (RADIANT-2), and pancreatic neuroendocrine tumors (RADIANT-3)] and TSC studies (EXIST-1 and EXIST-2). Data from solid tumor trials and TSC trials were analyzed separately. Results: The rate of stomatitis was 67% in the solid tumor trials (973/1455 patients) and 70% in the TSC trials (110/157 patients). Most stomatitis events were grade 1/2, with grade 3/4 events reported in only 9% (solid tumor trials) and 8% (TSC trials) of patients. Low TSC patient numbers prevented an in-depth evaluation of stomatitis and response. In the solid tumor trials, most first stomatitis episodes (89%; n ≥ 870) were observed within 8 weeks of starting everolimus. Patients with stomatitis occurring within 8 weeks of everolimus initiation had longer progression-free survival (PFS) than everolimus-treated patients without stomatitis in BOLERO-2 (8.5 versus 6.9 months, respectively; hazard ratio (HR), 0.78 [95% confidence interval (CI), 0.62-1.00]) and RADIANT-3 [13.9 versus 8.3 months, respectively; HR, 0.70 (95% CI, 0.48-1.04)]. A similar trend was observed in RECORD-1 [HR, 0.90 (95% CI, 0.66-1.22)] and RADIANT-2 [HR, 0.87 (95% CI, 0.61-1.22)] but not in BOLERO-3 [HR, 1.01 (95% CI, 0.75-1.36)]. Conclusions: Stomatitis did not adversely affect PFS, supporting the administration of everolimus in accordance with standard management guidelines.
AB - Background: Everolimus, an oral mammalian target of rapamycin (mTOR) inhibitor, is used to treat solid tumors and tuberous sclerosis complex (TSC). Stomatitis, an inflammation of the mucous membranes of the mouth, is a common adverse event associated with mTOR inhibitors, including everolimus. We conducted a meta-analysis of data from seven randomized, double-blind phase 3 clinical trials of everolimus to determine the clinical impact of stomatitis on efficacy and safety. Patients and methods: Data were pooled from the safety sets of solid tumor [breast cancer (BOLERO-2 and BOLERO-3), renal cell carcinoma (RECORD-1), carcinoid tumors (RADIANT-2), and pancreatic neuroendocrine tumors (RADIANT-3)] and TSC studies (EXIST-1 and EXIST-2). Data from solid tumor trials and TSC trials were analyzed separately. Results: The rate of stomatitis was 67% in the solid tumor trials (973/1455 patients) and 70% in the TSC trials (110/157 patients). Most stomatitis events were grade 1/2, with grade 3/4 events reported in only 9% (solid tumor trials) and 8% (TSC trials) of patients. Low TSC patient numbers prevented an in-depth evaluation of stomatitis and response. In the solid tumor trials, most first stomatitis episodes (89%; n ≥ 870) were observed within 8 weeks of starting everolimus. Patients with stomatitis occurring within 8 weeks of everolimus initiation had longer progression-free survival (PFS) than everolimus-treated patients without stomatitis in BOLERO-2 (8.5 versus 6.9 months, respectively; hazard ratio (HR), 0.78 [95% confidence interval (CI), 0.62-1.00]) and RADIANT-3 [13.9 versus 8.3 months, respectively; HR, 0.70 (95% CI, 0.48-1.04)]. A similar trend was observed in RECORD-1 [HR, 0.90 (95% CI, 0.66-1.22)] and RADIANT-2 [HR, 0.87 (95% CI, 0.61-1.22)] but not in BOLERO-3 [HR, 1.01 (95% CI, 0.75-1.36)]. Conclusions: Stomatitis did not adversely affect PFS, supporting the administration of everolimus in accordance with standard management guidelines.
KW - Breast cancer
KW - Everolimus
KW - Pancreatic neuroendocrine tumors
KW - Renal cell carcinoma
KW - Stomatitis
KW - Tuberous sclerosis complex
UR - http://www.scopus.com/inward/record.url?scp=84959903467&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84959903467&partnerID=8YFLogxK
U2 - 10.1093/annonc/mdv595
DO - 10.1093/annonc/mdv595
M3 - Article
C2 - 26759276
AN - SCOPUS:84959903467
SN - 0923-7534
VL - 27
SP - 519
EP - 525
JO - Annals of Oncology
JF - Annals of Oncology
IS - 3
M1 - mdv595
ER -