Effect of visceral metastases on the efficacy and safety of everolimus in postmenopausal women with advanced breast cancer: Subgroup analysis from the BOLERO-2 study Journal Article
| Authors: | Campone, M.; Bachelot, T.; Gnant, M.; Deleu, I.; Rugo, H. S.; Pistilli, B.; Noguchi, S.; Shtivelband, M.; Pritchard, K. I.; Provencher, L.; Burris, H. A. 3rd; Hart, L.; Melichar, B.; Hortobagyi, G. N.; Arena, F.; Baselga, J.; Panneerselvam, A.; Héniquez, A.; El-Hashimyt, M.; Taran, T.; Sahmoud, T.; Piccart, M. |
| Article Title: | Effect of visceral metastases on the efficacy and safety of everolimus in postmenopausal women with advanced breast cancer: Subgroup analysis from the BOLERO-2 study |
| Abstract: | Background Everolimus (EVE; an inhibitor of mammalian target of rapamycin [mTOR]) enhances treatment options for postmenopausal women with hormone-receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (ABC) who progress on a non-steroidal aromatase inhibitor (NSAI). This is especially true for patients with visceral disease, which is associated with poor prognosis. The BOLERO-2 (Breast cancer trial of OraL EveROlimus-2) trial showed that combination treatment with EVE and exemestane (EXE) versus placebo (PBO) + EXE prolonged progression-free survival (PFS) by both investigator (7.8 versus 3.2 months, respectively) and independent (11.0 versus 4.1 months, respectively) central assessment in postmenopausal women with HR+, HER2- ABC recurring/progressing during/after NSAI therapy. The BOLERO-2 trial included a substantial proportion of patients with visceral metastases (56%). Methods Prespecified exploratory subgroup analysis conducted to evaluate the efficacy and safety of EVE + EXE versus PBO + EXE in a prospectively defined subgroup of patients with visceral metastases. Findings At a median follow-up of 18 months, EVE + EXE significantly prolonged median PFS compared with PBO + EXE both in patients with visceral metastases (N = 406; 6.8 versus 2.8 months) and in those without visceral metastases (N = 318; 9.9 versus 4.2 months). Improvements in PFS with EVE + EXE versus PBO + EXE were also observed in patients with visceral metastases regardless of Eastern Cooperative Oncology Group performance status (ECOG PS). Patients with visceral metastases and ECOG PS 0 had a median PFS of 6.8 months with EVE + EXE versus 2.8 months with PBO + EXE. Among patients with visceral metastases and ECOG PS ≥1, EVE + EXE treatment more than tripled median PFS compared with PBO + EXE (6.8 versus 1.5 months). Interpretation Adding EVE to EXE markedly extended PFS by ≥4 months among patients with HR+ HER2- ABC regardless of the presence of visceral metastases. Funding Novartis. © 2013 Elsevier Ltd. All rights reserved. |
| Keywords: | adult; cancer survival; controlled study; treatment outcome; aged; middle aged; major clinical study; fatigue; cancer recurrence; placebo; advanced cancer; ascites; cancer combination chemotherapy; cancer growth; diarrhea; drug dose reduction; drug efficacy; drug safety; side effect; follow up; follow-up studies; prospective study; progression free survival; breast cancer; nausea; stomatitis; antineoplastic combined chemotherapy protocols; epidermal growth factor receptor 2; weight reduction; randomized controlled trials as topic; breast neoplasms; exemestane; coughing; hyperglycemia; rash; lung metastasis; clinical trials, phase iii as topic; breast carcinoma; neoplasm metastasis; pleura effusion; visceral metastasis; receptor, erbb-2; interstitial lung disease; headache; letrozole; randomization; anastrozole; hormone receptor; postmenopause; peritoneum metastasis; receptors, steroid; everolimus; hyperlipidemia; sirolimus; multicenter studies as topic; viscera; placebos; dysgeusia; exanthema; pleura metastasis; randomized controlled trial (topic); decreased appetite; phase 3 clinical trial (topic); kaplan-meier estimate; multicenter study (topic); androstadienes; advanced breast cancer; visceral metastases |
| Journal Title: | European Journal of Cancer |
| Volume: | 49 |
| Issue: | 12 |
| ISSN: | 0959-8049 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2013-08-01 |
| Start Page: | 2621 |
| End Page: | 2632 |
| Language: | English |
| DOI: | 10.1016/j.ejca.2013.04.011 |
| PROVIDER: | scopus |
| PUBMED: | 23735704 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 August 2013" - "CODEN: EJCAE" - "Source: Scopus" |
