Efficacy of everolimus with exemestane versus exemestane alone in Asian patients with HER2-negative, hormone-receptor-positive breast cancer in BOLERO-2.

Abstract

BACKGROUND:

The addition of mTOR inhibitor everolimus (EVE) to exemestane (EXE) was evaluated in an international, phase 3 study (BOLERO-2) in patients with hormone-receptor-positive (HR(+)) breast cancer refractory to letrozole or anastrozole. The safety and efficacy of anticancer treatments may be influenced by ethnicity (Sekine et al. in Br J Cancer 99:1757-62, 2008). Safety and efficacy results from Asian versus non-Asian patients in BOLERO-2 are reported.

METHODS:

Patients were randomized (2:1) to 10 mg/day EVE + EXE or placebo (PBO) + EXE. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rate, clinical benefit rate, and safety.

RESULTS:

Of 143 Asian patients, 98 received EVE + EXE and 45 received PBO + EXE. Treatment with EVE + EXE significantly improved median PFS versus PBO + EXE among Asian patients by 38 % (HR = 0.62; 95 % CI, 0.41-0.94). Median PFS was also improved among non-Asian patients by 59 % (HR = 0.41; 95 % CI, 0.33-0.50). Median PFS duration among EVE-treated Asian patients was 8.48 versus 4.14 months for PBO + EXE, and 7.33 versus 2.83 months, respectively, in non-Asian patients. The most common grade 3/4 adverse events (stomatitis, anemia, elevated liver enzymes, hyperglycemia, and dyspnea) occurred at similar frequencies in Asian and non-Asian patients. Grade 1/2 interstitial lung disease occurred more frequently in Asian patients. Quality of life was similar between treatment arms in Asian patients.

CONCLUSION:

Adding EVE to EXE provided substantial clinical benefit in both Asian and non-Asian patients with similar safety profiles. This combination represents an improvement in the management of postmenopausal women with HR(+)/HER2(-) advanced breast cancer progressing on nonsteroidal aromatase inhibitors, regardless of ethnicity.

• Authors: Shinzaburo Noguchi, Norikazu Masuda, Hiroji Iwata, Hirofumi Mukai, Jun Horiguchi, Puttisak Puttawibul, Vichien Srimuninnimit, Yutaka Tokuda, Katsumasa Kuroi, Hirotaka Iwase, Hideo Inaji, Shozo Ohsumi, Woo-Chul Noh, Takahiro Nakayama, Shinji Ohno, Yoshiaki Rai, Byeong-Woo Park, Ashok Panneerselvam, Mona El-Hashimy, Tetiana Taran, Tarek Sahmoud, Yoshinori Ito
• Journal: Breast cancer (Tokyo, Japan) (Breast Cancer) Vol. 21 Issue 6 Pg. 703-14 (Nov 2014) ISSN: 1880-4233 [Electronic] Japan
• PMID: 23404211 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Androstadienes
• Everolimus
• MTOR protein, human
• ERBB2 protein, human
• Receptor, ErbB-2
• TOR Serine-Threonine Kinases
• exemestane
• Sirolimus

Topics

• Adult
• Aged
• Androstadienes (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Asian People
• Breast Neoplasms (drug therapy, metabolism)
• Everolimus
• Female
• Humans
• Middle Aged
• Quality of Life
• Receptor, ErbB-2 (metabolism)
• Sirolimus (administration & dosage, adverse effects, analogs & derivatives, pharmacology)
• TOR Serine-Threonine Kinases (antagonists & inhibitors)
• Treatment Outcome