Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial
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- Cristina Saura
- Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), SOLTI Breast Cancer Cooperative Group, Barcelona, Spain
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- Mafalda Oliveira
- Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), SOLTI Breast Cancer Cooperative Group, Barcelona, Spain
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- Yin-Hsun Feng
- Chi Mei Medical Centre, Liouying, Tainan, Taiwan and Tri-Service General Hospital, Taipei, Taiwan
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- Ming-Shen Dai
- Chi Mei Medical Centre, Liouying, Tainan, Taiwan and Tri-Service General Hospital, Taipei, Taiwan
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- Shang-Wen Chen
- Chi Mei Medical Centre, Liouying, Tainan, Taiwan and Tri-Service General Hospital, Taipei, Taiwan
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- Sara A. Hurvitz
- University of California Los Angeles/Jonsson Comprehensive Cancer Center, Los Angeles, CA
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- Sung-Bae Kim
- University of Ulsan College of Medicine, Seoul, Republic of Korea
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- Beverly Moy
- Massachusetts General Hospital Cancer Center, Boston, MA
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- Suzette Delaloge
- Gustave Roussy, Villejuif, France
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- William Gradishar
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL
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- Norikazu Masuda
- National Hospital Organization, Osaka National Hospital, Osaka, Japan
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- Marketa Palacova
- Masaryk Memorial Cancer Institute, Brno, Czech Republic
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- Maureen E. Trudeau
- Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
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- Johanna Mattson
- Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland
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- Yoon Sim Yap
- National Cancer Centre Singapore, Singapore
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- Ming-Feng Hou
- Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
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- Michelino De Laurentiis
- National Cancer Institute Fondazione Pascale, Napoli, Italy
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- Yu-Min Yeh
- National Cheng Kung University, Tainan, Taiwan
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- Hong-Tai Chang
- Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
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- Thomas Yau
- Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong
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- Hans Wildiers
- University Hospitals Leuven, Leuven, Belgium
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- Barbara Haley
- UT Southwestern Medical Center, Dallas, TX
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- Daniele Fagnani
- ASST di Vimercate, Vimercate, Italy
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- Yen-Shen Lu
- National Taiwan University Hospital, Taipei City, Taiwan
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- John Crown
- St Vincent’s University Hospital, Dublin, Ireland
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- Johnson Lin
- MacKay Memorial Hospital, Taipei, Taiwan
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- Masato Takahashi
- National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan
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- Toshimi Takano
- Toranomon Hospital, Tokyo, Japan
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- Miki Yamaguchi
- Department of Breast Surgery, JCHO Kurume General Hospital, Kurume, Japan
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- Takaaki Fujii
- Graduate School of Medicine, Gunma University, Gunma, Japan
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- Bin Yao
- Puma Biotechnology, Los Angeles, CA
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- Judith Bebchuk
- Puma Biotechnology, Los Angeles, CA
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- Kiana Keyvanjah
- Puma Biotechnology, Los Angeles, CA
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- Richard Bryce
- Puma Biotechnology, Los Angeles, CA
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- Adam Brufsky
- Magee-Womens Hospital of UPMC, Pittsburgh, PA
Description
<jats:sec><jats:title>PURPOSE</jats:title><jats:p> NALA (ClinicalTrials.gov identifier: NCT01808573 ) is a randomized, active-controlled, phase III trial comparing neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), plus capecitabine (N+C) against lapatinib, a reversible dual TKI, plus capecitabine (L+C) in patients with centrally confirmed HER2-positive, metastatic breast cancer (MBC) with ≥ 2 previous HER2-directed MBC regimens. </jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p> Patients, including those with stable, asymptomatic CNS disease, were randomly assigned 1:1 to neratinib (240 mg once every day) plus capecitabine (750 mg/m<jats:sup>2</jats:sup> twice a day 14 d/21 d) with loperamide prophylaxis, or to lapatinib (1,250 mg once every day) plus capecitabine (1,000 mg/m<jats:sup>2</jats:sup> twice a day 14 d/21 d). Coprimary end points were centrally confirmed progression-free survival (PFS) and overall survival (OS). NALA was considered positive if either primary end point was met (α split between end points). Secondary end points were time to CNS disease intervention, investigator-assessed PFS, objective response rate (ORR), duration of response (DoR), clinical benefit rate, safety, and health-related quality of life (HRQoL). </jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p> A total of 621 patients from 28 countries were randomly assigned (N+C, n = 307; L+C, n = 314). Centrally reviewed PFS was improved with N+C (hazard ratio [HR], 0.76; 95% CI, 0.63 to 0.93; stratified log-rank P = .0059). The OS HR was 0.88 (95% CI, 0.72 to 1.07; P = .2098). Fewer interventions for CNS disease occurred with N+C versus L+C (cumulative incidence, 22.8% v 29.2%; P = .043). ORRs were N+C 32.8% (95% CI, 27.1 to 38.9) and L+C 26.7% (95% CI, 21.5 to 32.4; P = .1201); median DoR was 8.5 versus 5.6 months, respectively (HR, 0.50; 95% CI, 0.33 to 0.74; P = .0004). The most common all-grade adverse events were diarrhea (N+C 83% v L+C 66%) and nausea (53% v 42%). Discontinuation rates and HRQoL were similar between groups. </jats:p></jats:sec><jats:sec><jats:title>CONCLUSION</jats:title><jats:p> N+C significantly improved PFS and time to intervention for CNS disease versus L+C. No new N+C safety signals were observed. </jats:p></jats:sec>
Journal
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- Journal of Clinical Oncology
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Journal of Clinical Oncology 38 (27), 3138-3149, 2020-09-20
American Society of Clinical Oncology (ASCO)
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Details 詳細情報について
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- CRID
- 1360861712125796992
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- ISSN
- 15277755
- 0732183X
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- Data Source
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- Crossref