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

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, 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

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.

Trial registration: ClinicalTrials.gov NCT00863655.

Figures

Fig. 1
Fig. 1
CONSORT flowchart. ITT intention-to-treat. Ongoing treatment refers to those patients at time of cutoff for this analysis. Note that disease progression events in this figure are those that resulted in treatment discontinuation
Fig. 2
Fig. 2
Kaplan–Meier analyses of progression-free survival in a Asian and b non-Asian patients with advanced breast cancer. CI confidence interval, EVE everolimus, EXE exemestane, HR hazard ratio, PBO placebo
Fig. 3
Fig. 3
Forest plot of progression-free survival subgroup analysis by region and ethnicity. Subsets were prespecified in the analysis plan. Data from 18-months’ median follow-up. EVE everolimus, EXE exemestane, HR hazard ratio, PBO placebo, PFS progression-free survival
Fig. 4
Fig. 4
Time to deterioration in EORTC QLQ-C30 (5 % decrease from baseline). CI confidence interval, EORTC QLQ-C30 European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, EVE everolimus, EXE exemestane, PBO placebo, TTD time to definitive deterioration

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Source: PubMed

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