Incidence and time course of everolimus-related adverse events in postmenopausal women with hormone receptor-positive advanced breast cancer: insights from BOLERO-2.

BackgroundIn 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 methodsPatients 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.ResultsThe 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%).ConclusionsMost 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.Trial registration numberNCT00863655

Comparison of 6q25 Breast Cancer Hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC)

Peer reviewe

Incidence and time course of everolimus-related adverse events in postmenopausal women with hormone receptor-positive advanced breast cancer: insights from BOLERO-2.

BackgroundIn 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 methodsPatients 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.ResultsThe 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%).ConclusionsMost 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.Trial registration numberNCT00863655

Clinical management and resolution of stomatitis in BOLERO-2

558 Background: In BOLERO-2, adding everolimus (EVE) to exemestane (EXE) more than doubled progression-free survival without affecting quality of life vs EXE alone in postmenopausal women with hormone-receptor–positive advanced breast cancer who had recurrence or progression on/after nonsteroidal aromatase inhibitor therapy. Although mTOR inhibitors are generally well tolerated, stomatitis is one of their most clinically relevant and potentially dose-limiting toxicities (Sonis Cancer2010). The incidence, grade, and clinical course of stomatitis among patients (pts) participating in the BOLERO-2 study are described. Methods: Pts were randomized 2:1 to receive EVE+EXE or placebo (PBO)+EXE. Stomatitis incidence, severity, consequent dose interruptions/adjustments, study drug discontinuations, and time to resolution were recorded. Results: The median duration of EVE+EXE treatment exposure was 30 wk (range, 1-123 wk). Stomatitis (any grade) occurred more frequently with EVE+EXE than with PBO+EXE (59% vs 12%, respectively). Grade 3 stomatitis occurred in 8% vs 1% of pts receiving EVE+EXE vs PBO+EXE, respectively; no grade 4 was reported. Onset of grade ≥2 stomatitis after treatment initiation was earlier in the EVE+EXE arm vs the PBO+EXE arm: median time was 15d vs 24d, respectively. In the EVE+EXE arm, 97% of pts with grade 3 stomatitis (n=38) improved to ≤1 after a median of 13 d. Complete resolution was observed in 82% of these pts after a median of 38 d. In the PBO+EXE arm, all pts with grade 3 stomatitis (n=2) improved to ≤1 after a median of 18 d. Complete resolution was observed after a median of 29 d. Overall, 24% of pts in the EVE+EXE arm required dose interruptions/adjustments vs 1% of pts in the PBO+EXE arm, and 3% of pts (n=13) discontinued EVE+EXE vs <1% of pts (n=1) discontinuing PBO+EXE, all related to stomatitis. Conclusions: The BOLERO-2 data foster a new era of combining targeted and endocrine therapies. In the study, treatment-emergent stomatitis was of mild to moderate intensity, occurred shortly after treatment initiation, and was generally reversible. Most incidents were successfully managed with palliative interventions and temporary dose modifications. Oral hygiene and other preventive measures are recommended. Clinical trial information: NCT00863655

Seroma Formation after Mastectomy: Pathogenesis and Prevention

Post mastectomy seroma remains an unresolved quandary as the risk factors for its formation have still not been identified. Seromas of the axillary space following breast surgery can lead to significant morbidity and delay in the initiation of adjuvant therapy. Various techniques and their modifications have been practiced and published in English literature, but there seems to be no consensus. In this article, all aspects of seroma formation from pathogenesis to prevention including drug therapies have been discussed