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

• DOI: 10.1007/s12282-013-0444-8
• Publication Date: 2013-02-12T03:41:46Z
• Authors: Shinzaburo Noguchi; Norikazu Masuda; Hiroji Iwata; Hirofumi Mukai; Jun Horiguchi; Puttisak Puttawibul; Vichien Srimuninn...; 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
• Keywords: Androstadienes/adverse effects; Asian Continental Ancestry Group; Adult; Receptor, ErbB-2; 610; Breast Neoplasms; Sirolimus/administration & dosage; 03 medical and health sciences; 0302 clinical medicine; Asian People; Antineoplastic Combined Chemotherapy Protocols; Humans; Androstadienes/administration & dosage; Pharmacology (medical); Everolimus; Aged; Sirolimus; TOR Serine-Threonine Kinases/antagonists & inhibitors; Antineoplastic Combined Chemotherapy Protocols/adverse effects; TOR Serine-Threonine Kinases; Sirolimus/pharmacology; Middle Aged; 3. Good health; Androstadienes; Treatment Outcome; Sirolimus/adverse effects; Oncology; Breast Neoplasms/metabolism; Radiology Nuclear Medicine and imaging; Breast Neoplasms/drug therapy*; Quality of Life; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*; ErbB-2/metabolism; Original Article; Female; Sirolimus/analogs & derivatives; Receptor

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.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.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.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.