Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial

被引：451

作者：

Saura, Cristina ^{[1
]}

Oliveira, Mafalda ^{[1
]}

Feng, Yin-Hsun ^{[2
,3
]}

Dai, Ming-Shen ^{[2
,3
]}

Chen, Shang-Wen ^{[2
,3
]}

Hurvitz, Sara A. ^{[4
]}

Kim, Sung-Bae ^{[5
]}

Moy, Beverly ^{[6
]}

Delaloge, Suzette ^{[7
]}

Gradishar, William ^{[8
]}

Masuda, Norikazu ^{[9
]}

Palacova, Marketa ^{[10
]}

Trudeau, Maureen E. ^{[11
]}

Mattson, Johanna ^{[12
]}

Yap, Yoon Sim ^{[13
]}

Hou, Ming-Feng ^{[14
]}

De Laurentiis, Michelino ^{[15
]}

Yeh, Yu-Min ^{[16
]}

Chang, Hong-Tai ^{[17
]}

Yau, Thomas ^{[18
]}

Wildiers, Hans ^{[19
,20
]}

Haley, Barbara ^{[21
]}

Fagnani, Daniele ^{[22
]}

Lu, Yen-Shen ^{[23
]}

Crown, John ^{[24
]}

Lin, Johnson ^{[25
]}

Takahashi, Masato ^{[26
]}

Takano, Toshimi ^{[27
]}

Yamaguchi, Miki ^{[28
]}

Fujii, Takaaki ^{[29
]}

Yao, Bin ^{[30
]}

Bebchuk, Judith ^{[30
]}

Keyvanjah, Kiana ^{[30
]}

Bryce, Richard ^{[30
]}

Brufsky, Adam ^{[31
]}

机构：

[1] Vall dHebron Univ Hosp, Vail dHebron Inst Oncol VHIO, SOLTI Breast Canc Cooperat Grp, Barcelona, Spain

[2] Chi Mei Med Ctr, Tainan, Taiwan

[3] Triserv Gen Hosp, Taipei, Taiwan

[4] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA

[5] Univ Ulsan, Coll Med, Seoul, South Korea

[6] Massachusetts Gen Hosp, Canc Ctr, Boston, MA 02114 USA

[7] Gustave Roussy, Villejuif, France

[8] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA

[9] Natl Hosp Org, Osaka Natl Hosp, Osaka, Japan

[10] Masaryk Mem Canc Inst, Brno, Czech Republic

[11] Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada

[12] Helsinki Univ Hosp, Comprehens Canc Ctr, Helsinki, Finland

[13] Natl Canc Ctr Singapore, Singapore, Singapore

[14] Kaohsiung Med Univ Hosp, Kaohsiung, Taiwan

[15] Natl Canc Inst Fdn Pascale, Naples, Italy

[16] Natl Cheng Kung Univ, Tainan, Taiwan

[17] Kaohsiung Vet Gen Hosp, Kaohsiung, Taiwan

[18] Univ Hong Kong, Li Ka Shing Fac Med, Hong Kong, Peoples R China

[19] Univ Hosp Leuven, Leuven, Belgium

[20] Katholieke Univ Leuven, Dept Oncol, Leuven, Belgium

[21] UT Southwestern Med Ctr, Dallas, TX USA

[22] ASST Vimercate, Vimercate, Italy

[23] Natl Taiwan Univ Hosp, Taipei, Taiwan

[24] St Vincents Univ Hosp, Dublin, Ireland

[25] MacKay Mem Hosp, Taipei, Taiwan

[26] Natl Hosp Org Hokkaido Canc Ctr, Sapporo, Hokkaido, Japan

[27] Toranomon Gen Hosp, Tokyo, Japan

[28] JCHO Kurume Gen Hosp, Dept Breast Surg, Kurume, Fukuoka, Japan

[29] Gunma Univ, Grad Sch Med, Gunma, Japan

[30] Puma Biotechnol, Los Angeles, CA USA

[31] UPMC, Magee Womens Hosp, Pittsburgh, PA USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2020年 / 38卷 / 27期

关键词：

TRASTUZUMAB EMTANSINE; OPEN-LABEL; RECEPTOR; THERAPY; COMBINATION;

D O I：

10.1200/JCO.20.00147

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSE 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. METHODS 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(2) 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(2) 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 (alpha 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). RESULTS A total of 621 patients from 28 countries were randomly assigned (N+C, n = 307; L+C, n 5 314). Centrally reviewed PFS was improved with N+C (hazard ratio [HR], 0.76; 95% CI, 0.63 to 0.93; stratified logrank 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 5.1201); 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. CONCLUSION N+C significantly improved PFS and time to intervention for CNS disease versus L+C. No new N+C safety signals were observed. (C) 2020 by American Society of Clinical Oncology

引用

页码：3138 / +

页数：23

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