Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial
| Autor: | Cristina Saura, Suzette Delaloge, Sung Bae Kim, Mafalda Oliveira, Yen-Shen Lu, Bin Yao, John Crown, Ming-Shen Dai, Hong-Tai Chang, Thomas Yau, Takaaki Fujii, Nala Investigators, Daniele Fagnani, Maureen E. Trudeau, Ming-Feng Hou, William J. Gradishar, Johanna Mattson, Marketa Palacova, Barbara Haley, Masato Takahashi, Beverly Moy, Yu-Min Yeh, Richard Bryce, Kiana Keyvanjah, Miki Yamaguchi, Shang Wen Chen, Judith Bebchuk, Adam Brufsky, Norikazu Masuda, Michelino De Laurentiis, Yin-Hsun Feng, Johnson Lin, Toshimi Takano, Sara A. Hurvitz, Hans Wildiers, Yoon Sim Yap |
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| Přispěvatelé: | Institut Català de la Salut, [Saura C, Oliveira M] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. SOLTI Breast Cancer Cooperative Group, Barcelona, Spain. [Feng YH, Dai MS, Chen SW] Chi Mei Medical Centre, Liouying, Tainan, Taiwan and Tri-Service General Hospital, Taipei, Taiwan. [Hurvitz SA] University of California Los Angeles/Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA, Vall d'Hebron Barcelona Hospital Campus, Saura, C., Oliveira, M., Feng, Y. -H., Dai, M. -S., Chen, S. -W., Hurvitz, S. A., Kim, S. -B., Moy, B., Delaloge, S., Gradishar, W., Masuda, N., Palacova, M., Trudeau, M. E., Mattson, J., Yap, Y. S., Hou, M. -F., De Laurentiis, M., Yeh, Y. -M., Chang, H. -T., Yau, T., Wildiers, H., Haley, B., Fagnani, D., Lu, Y. -S., Crown, J., Lin, J., Takahashi, M., Takano, T., Yamaguchi, M., Fujii, T., Yao, B., Bebchuk, J., Keyvanjah, K., Bryce, R., Brufsky, A. |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology Male Cancer Research Receptor ErbB-2 Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES] Quinoline Medicaments antineoplàstics - Ús terapèutic Kaplan-Meier Estimate THERAPY Tyrosine-kinase inhibitor law.invention chemistry.chemical_compound ErbB-2 0302 clinical medicine Randomized controlled trial Mama - Càncer law Antineoplastic Combined Chemotherapy Protocols Other subheadings::/therapeutic use [Other subheadings] neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES] Brain Neoplasms Nausea ORIGINAL REPORTS Middle Aged OPEN-LABEL Metastatic breast cancer Progression-Free Survival 3. Good health Survival Rate TRASTUZUMAB EMTANSINE 030220 oncology & carcinogenesis Neratinib Retreatment Quinolines Female Life Sciences & Biomedicine Breast Neoplasm medicine.drug Human Diarrhea medicine.medical_specialty medicine.drug_class Clinical Sciences Oncology and Carcinogenesis Breast Neoplasms Lapatinib Breast Neoplasms Male Capecitabine Brain Neoplasm 03 medical and health sciences Internal medicine Breast Cancer medicine Humans Oncology & Carcinogenesis Progression-free survival COMBINATION terapéutica::protocolos clínicos::protocolos antineoplásicos::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] Aged Science & Technology Antineoplastic Combined Chemotherapy Protocol RECEPTOR business.industry Otros calificadores::/uso terapéutico [Otros calificadores] Therapeutics::Clinical Protocols::Antineoplastic Protocols::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] medicine.disease 030104 developmental biology chemistry Trastuzumab emtansine Quality of Life NALA Investigators business |
| Zdroj: | Scientia Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol 38, iss 27 Journal of Clinical Oncology |
| Popis: | 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/m2 twice a day 14 d/21 d) with loperamide prophylaxis, or to lapatinib (1,250 mg once every day) plus capecitabine (1,000 mg/m2 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). RESULTS 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. CONCLUSION N+C significantly improved PFS and time to intervention for CNS disease versus L+C. No new N+C safety signals were observed. |
| Databáze: | OpenAIRE |
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