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Breast Cancer Research
Published in: Breast Cancer Research 1/2017

Open Access 01-12-2017 | Research article

Efficacy and safety of everolimus in combination with trastuzumab and paclitaxel in Asian patients with HER2+ advanced breast cancer in BOLERO-1

Authors: Masakazu Toi, Zhimin Shao, Sara Hurvitz, Ling-Ming Tseng, Qingyuan Zhang, Kunwei Shen, Donggeng Liu, Jifeng Feng, Binghe Xu, Xiaojia Wang, Keun Seok Lee, Ting Ying Ng, Antonia Ridolfi, Florence Noel-baron, Francois Ringeisen, Zefei Jiang

Published in: Breast Cancer Research | Issue 1/2017

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Abstract

Background

The current exploratory analysis was performed to evaluate the efficacy and safety of everolimus for treatment of human epidermal growth factor receptor 2-positive (HER2+) advanced breast cancer in the Asian subset of patients in the BOLERO-1 trial.

Methods

Postmenopausal women with HER2+ advanced breast cancer, who had not received systemic therapy for advanced disease, were randomized 2:1 to receive everolimus or placebo, plus trastuzumab and paclitaxel. The two primary end points were investigator-assessed progression-free survival (PFS) in the full population and in the hormone receptor-negative (HR–) subpopulation. Secondary end points included assessment of the objective response rate, the clinical benefit rate, and safety.

Results

In the Asian subset, median PFS was similar in the everolimus (n = 198) and placebo (n = 105) arms in the full analysis set (hazard ratio = 0.82 (95% CI 0.61–1.11)). In the HR– subpopulation, everolimus prolonged median PFS by 10.97 months vs placebo (25.46 vs 14.49 months; hazard ratio = 0.48 (95% CI 0.29–0.79)). In the everolimus arm of the Asian subset, the most common adverse events of any grade were stomatitis (62.2%), diarrhea (48.0%), rash (43.4%) and neutropenia (42.3%). Neutropenia (grade 3: 27.6%; grade 4: 4.6%) and decreased neutrophil count (grade 3: 11.2%; grade 4: 3.6%) were the most frequent grade 3/4 adverse events. Serious adverse events included pneumonia (5.1%), pneumonitis (3.1%), and interstitial lung disease (3.1%). There were three deaths (1.5%) during treatment in the everolimus arm vs none in the placebo arm.

Conclusions

The efficacy and safety of everolimus plus trastuzumab and paclitaxel as first-line treatment for HER2+ advanced breast cancer in the Asian subset was consistent with that reported previously in the overall population.

Trial registration

ClinicalTrials.gov, NCT00876395. Registered on 2 April 2009.
Appendix
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Literature
1.
Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365(14):1273–83.CrossRefPubMedPubMedCentral
2.
Witton CJ, Reeves JR, Going JJ, Cooke TG, Bartlett JM. Expression of the HER1-4 family of receptor tyrosine kinases in breast cancer. J Pathol. 2003;200(3):290–7.CrossRefPubMed
3.
Singh JC, Jhaveri K, Esteva FJ. HER2-positive advanced breast cancer: optimizing patient outcomes and opportunities for drug development. Br J Cancer. 2014;111(10):1888–98.CrossRefPubMedPubMedCentral
4.
Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gomez H, Dinh P, Fauria K, Van Dooren V, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012;379(9816):633–40.CrossRefPubMed
5.
Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la Haba-Rodriguez J, Im SA, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(1):25–32.CrossRefPubMed
6.
Romond EH, Perez EA, Bryant J, Suman VJ, Geyer Jr CE, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353(16):1673–84.CrossRefPubMed
7.
Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783–92.CrossRefPubMed
8.
Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Dieras V, Guardino E, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367(19):1783–91.CrossRefPubMedPubMedCentral
9.
10.
Subbiah IM, Gonzalez-Angulo AM. Advances and future directions in the targeting of HER2-positive breast cancer: implications for the future. Curr Treat Options in Oncol. 2014;15(1):41–54.CrossRef
11.
Dave B, Migliaccio I, Gutierrez MC, Wu MF, Chamness GC, Wong H, Narasanna A, Chakrabarty A, Hilsenbeck SG, Huang J, et al. Loss of phosphatase and tensin homolog or phosphoinositol-3 kinase activation and response to trastuzumab or lapatinib in human epidermal growth factor receptor 2-overexpressing locally advanced breast cancers. J Clin Oncol. 2011;29(2):166–73.CrossRefPubMed
12.
Esteva FJ, Guo H, Zhang S, Santa-Maria C, Stone S, Lanchbury JS, Sahin AA, Hortobagyi GN, Yu D. PTEN, PIK3CA, p-AKT, and p-p70S6K status: association with trastuzumab response and survival in patients with HER2-positive metastatic breast cancer. Am J Pathol. 2010;177(4):1647–56.CrossRefPubMedPubMedCentral
13.
Lu CH, Wyszomierski SL, Tseng LM, Sun MH, Lan KH, Neal CL, Mills GB, Hortobagyi GN, Esteva FJ, Yu D. Preclinical testing of clinically applicable strategies for overcoming trastuzumab resistance caused by PTEN deficiency. Clin Cancer Res. 2007;13(19):5883–8.CrossRefPubMed
14.
Morrow PK, Wulf GM, Ensor J, Booser DJ, Moore JA, Flores PR, Xiong Y, Zhang S, Krop IE, Winer EP, et al. Phase I/II study of trastuzumab in combination with everolimus (RAD001) in patients with HER2-overexpressing metastatic breast cancer who progressed on trastuzumab-based therapy. J Clin Oncol. 2011;29(23):3126–32.CrossRefPubMedPubMedCentral
15.
Andre F, O’Regan R, Ozguroglu M, Toi M, Xu B, Jerusalem G, Masuda N, Wilks S, Arena F, Isaacs C, et al. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014;15(6):580–91.CrossRefPubMed
16.
Hurvitz SA, Andre F, Jiang Z, Shao Z, Mano MS, Neciosup SP, Tseng LM, Zhang Q, Shen K, Liu D, et al. Combination of everolimus with trastuzumab plus paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer (BOLERO-1): a phase 3, randomised, double-blind, multicentre trial. Lancet Oncol. 2015;16(7):816–29.CrossRefPubMed
17.
Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366(2):109–19.CrossRefPubMed
18.
Ling WH, Lee SC. Inter-ethnic differences–how important is it in cancer treatment? Ann Acad Med Singap. 2011;40(8):356–61.PubMed
19.
Noguchi S, Masuda N, Iwata H, Mukai H, Horiguchi J, Puttawibul P, Srimuninnimit V, Tokuda Y, Kuroi K, Iwase H, et al. Efficacy of everolimus with exemestane versus exemestane alone in Asian patients with HER2-negative, hormone-receptor-positive breast cancer in BOLERO-2. Breast Cancer. 2014;21(6):703–14.CrossRefPubMed
20.
Okamoto I, Doi T, Ohtsu A, Miyazaki M, Tsuya A, Kurei K, Kobayashi K, Nakagawa K. Phase I clinical and pharmacokinetic study of RAD001 (everolimus) administered daily to Japanese patients with advanced solid tumors. Jpn J Clin Oncol. 2010;40(1):17–23.CrossRefPubMed
21.
22.
Xie HG, Kim RB, Wood AJ, Stein CM. Molecular basis of ethnic differences in drug disposition and response. Annu Rev Pharmacol Toxicol. 2001;41:815–50.CrossRefPubMed
23.
Han HS, Reis IM, Zhao W, Kuroi K, Toi M, Suzuki E, Syme R, Chow L, Yip AY, Gluck S. Racial differences in acute toxicities of neoadjuvant or adjuvant chemotherapy in patients with early-stage breast cancer. Eur J Cancer. 2011;47(17):2537–45.CrossRefPubMed
24.
Kim HS, Hong MH, Kim K, Shin SJ, Ahn JB, Jeung HC, Chung HC, Koh Y, Lee SH, Bang YJ, et al. Sunitinib for Asian patients with advanced renal cell carcinoma: a comparable efficacy with different toxicity profiles. Oncology. 2011;80(5-6):395–405.CrossRefPubMed
25.
Xu B, Zhang XQ, Chi HD, Liu Z, Quinlivan M, Orlando M. Consistent efficacy and safety of gemcitabine-paclitaxel in patients with metastatic breast cancer: a retrospective comparison of East Asian and global studies. Asia Pac J Clin Oncol. 2014;10(4):330–9.CrossRefPubMed
26.
Hasegawa Y, Kawaguchi T, Kubo A, Ando M, Shiraishi J, Isa S, Tsuji T, Tsujino K, Ou SH, Nakagawa K, et al. Ethnic difference in hematological toxicity in patients with non-small cell lung cancer treated with chemotherapy: a pooled analysis on Asian versus non-Asian in phase II and III clinical trials. J Thorac Oncol. 2011;6(11):1881–8.CrossRefPubMed
Metadata
Title
Efficacy and safety of everolimus in combination with trastuzumab and paclitaxel in Asian patients with HER2+ advanced breast cancer in BOLERO-1
Authors
Masakazu Toi
Zhimin Shao
Sara Hurvitz
Ling-Ming Tseng
Qingyuan Zhang
Kunwei Shen
Donggeng Liu
Jifeng Feng
Binghe Xu
Xiaojia Wang
Keun Seok Lee
Ting Ying Ng
Antonia Ridolfi
Florence Noel-baron
Francois Ringeisen
Zefei Jiang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2017
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-017-0839-0

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