Abstract
Background: In the BOLERO-2 trial, everolimus (EVE), an inhibitor of mammalian target of rapamycin, demonstrated significant clinical benefit with an acceptable safety profile when administered with exemestane (EXE) in postmenopausal women with hormone receptor-positive (HR+) advanced breast cancer. We report on the incidence, time course, severity, and resolution of treatment-emergent adverse events (AEs) as well as incidence of dose modifications during the extended follow-up of this study. Patients and methods: Patients were randomized (2:1) to receive EVE 10 mg/day or placebo (PBO), with open-label EXE 25 mg/day (n = 724). The primary end point was progression-free survival. Secondary end points included overall survival, objective response rate, and safety. Safety evaluations included recording of AEs, laboratory values, dose interruptions/adjustments, and study drug discontinuations. Results: The safety population comprised 720 patients (EVE + EXE, 482; PBO + EXE, 238). The median follow-up was 18 months. Class effect toxicities, including stomatitis, pneumonitis, and hyperglycemia, were generally of mild or moderate severity and occurred relatively early after treatment initiation (except pneumonitis); incidence tapered off thereafter. EVE dose reduction and interruption (360 and 705 events, respectively) required for AE management were independent of patient age. The median duration of dose interruption was 7 days. Discontinuation of both study drugs because of AEs was higher with EVE + EXE (9%) versus PBO + EXE (3%).Conclusions: Most EVE associated AEs occur soon after initiation of therapy, are typically of mild or moderate severity, and are generally manageable with dose reduction and interruption. Discontinuation due to toxicity was uncommon. Understanding the time course of class-effect AEs will help inform preventive and monitoring strategies as well as patient education.
| Original language | English (US) |
|---|---|
| Article number | mdu009 |
| Pages (from-to) | 808-815 |
| Number of pages | 8 |
| Journal | Annals of Oncology |
| Volume | 25 |
| Issue number | 4 |
| DOIs | |
| State | Published - 2014 |
| Externally published | Yes |
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Keywords
- Advanced breast cancer
- Everolimus
- Mammalian target of rapamycin (mTOR)
- Safety
ASJC Scopus subject areas
- Oncology
- Hematology
- Medicine(all)
Cite this
Incidence and time course of everolimus-related adverse events in postmenopausal women with hormone receptor-positive advanced breast cancer : Insights from BOLERO-2. / Rugo, H. S.; Pritchard, K. I.; Gnant, M.; Noguchi, S.; Piccart, M.; Hortobagyi, G.; Baselga, J.; Perez, Alejandra; Geberth, M.; Csoszi, T.; Chouinard, E.; Srimuninnimit, V.; Puttawibul, P.; Eakle, J.; Feng, W.; Bauly, H.; El-hashimy, M.; Taran, T.; Burris, H. A.
In: Annals of Oncology, Vol. 25, No. 4, mdu009, 2014, p. 808-815.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Incidence and time course of everolimus-related adverse events in postmenopausal women with hormone receptor-positive advanced breast cancer
T2 - Insights from BOLERO-2
AU - Rugo, H. S.
AU - Pritchard, K. I.
AU - Gnant, M.
AU - Noguchi, S.
AU - Piccart, M.
AU - Hortobagyi, G.
AU - Baselga, J.
AU - Perez, Alejandra
AU - Geberth, M.
AU - Csoszi, T.
AU - Chouinard, E.
AU - Srimuninnimit, V.
AU - Puttawibul, P.
AU - Eakle, J.
AU - Feng, W.
AU - Bauly, H.
AU - El-hashimy, M.
AU - Taran, T.
AU - Burris, H. A.
PY - 2014
Y1 - 2014
N2 - Background: In the BOLERO-2 trial, everolimus (EVE), an inhibitor of mammalian target of rapamycin, demonstrated significant clinical benefit with an acceptable safety profile when administered with exemestane (EXE) in postmenopausal women with hormone receptor-positive (HR+) advanced breast cancer. We report on the incidence, time course, severity, and resolution of treatment-emergent adverse events (AEs) as well as incidence of dose modifications during the extended follow-up of this study. Patients and methods: Patients were randomized (2:1) to receive EVE 10 mg/day or placebo (PBO), with open-label EXE 25 mg/day (n = 724). The primary end point was progression-free survival. Secondary end points included overall survival, objective response rate, and safety. Safety evaluations included recording of AEs, laboratory values, dose interruptions/adjustments, and study drug discontinuations. Results: The safety population comprised 720 patients (EVE + EXE, 482; PBO + EXE, 238). The median follow-up was 18 months. Class effect toxicities, including stomatitis, pneumonitis, and hyperglycemia, were generally of mild or moderate severity and occurred relatively early after treatment initiation (except pneumonitis); incidence tapered off thereafter. EVE dose reduction and interruption (360 and 705 events, respectively) required for AE management were independent of patient age. The median duration of dose interruption was 7 days. Discontinuation of both study drugs because of AEs was higher with EVE + EXE (9%) versus PBO + EXE (3%).Conclusions: Most EVE associated AEs occur soon after initiation of therapy, are typically of mild or moderate severity, and are generally manageable with dose reduction and interruption. Discontinuation due to toxicity was uncommon. Understanding the time course of class-effect AEs will help inform preventive and monitoring strategies as well as patient education.
AB - Background: In the BOLERO-2 trial, everolimus (EVE), an inhibitor of mammalian target of rapamycin, demonstrated significant clinical benefit with an acceptable safety profile when administered with exemestane (EXE) in postmenopausal women with hormone receptor-positive (HR+) advanced breast cancer. We report on the incidence, time course, severity, and resolution of treatment-emergent adverse events (AEs) as well as incidence of dose modifications during the extended follow-up of this study. Patients and methods: Patients were randomized (2:1) to receive EVE 10 mg/day or placebo (PBO), with open-label EXE 25 mg/day (n = 724). The primary end point was progression-free survival. Secondary end points included overall survival, objective response rate, and safety. Safety evaluations included recording of AEs, laboratory values, dose interruptions/adjustments, and study drug discontinuations. Results: The safety population comprised 720 patients (EVE + EXE, 482; PBO + EXE, 238). The median follow-up was 18 months. Class effect toxicities, including stomatitis, pneumonitis, and hyperglycemia, were generally of mild or moderate severity and occurred relatively early after treatment initiation (except pneumonitis); incidence tapered off thereafter. EVE dose reduction and interruption (360 and 705 events, respectively) required for AE management were independent of patient age. The median duration of dose interruption was 7 days. Discontinuation of both study drugs because of AEs was higher with EVE + EXE (9%) versus PBO + EXE (3%).Conclusions: Most EVE associated AEs occur soon after initiation of therapy, are typically of mild or moderate severity, and are generally manageable with dose reduction and interruption. Discontinuation due to toxicity was uncommon. Understanding the time course of class-effect AEs will help inform preventive and monitoring strategies as well as patient education.
KW - Advanced breast cancer
KW - Everolimus
KW - Mammalian target of rapamycin (mTOR)
KW - Safety
UR - http://www.scopus.com/inward/record.url?scp=84897102034&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84897102034&partnerID=8YFLogxK
U2 - 10.1093/annonc/mdu009
DO - 10.1093/annonc/mdu009
M3 - Article
C2 - 24615500
AN - SCOPUS:84897102034
VL - 25
SP - 808
EP - 815
JO - Annals of Oncology
JF - Annals of Oncology
SN - 0923-7534
IS - 4
M1 - mdu009
ER -