File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

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

TitleNeratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial
Authors
Keywordsabdominal infection
abdominal pain
acute kidney failure
adult
anemia
Issue Date2020
PublisherAmerican Society of Clinical Oncology. The Journal's web site is located at http://www.jco.org/
Citation
Journal of Clinical Oncology, 2020, v. 38 n. 27, p. 3138-3149 How to Cite?
AbstractPURPOSE: 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.
Persistent Identifierhttp://hdl.handle.net/10722/289768
ISSN
2020 Impact Factor: 44.544
2020 SCImago Journal Rankings: 10.482
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSaura, C-
dc.contributor.authorOliveira, M-
dc.contributor.authorFeng, YH-
dc.contributor.authorDai, MS-
dc.contributor.authorChen, SW-
dc.contributor.authorHurvitz, SA-
dc.contributor.authorKim, SB-
dc.contributor.authorMoy, B-
dc.contributor.authorDelaloge, S-
dc.contributor.authorGradishar, W-
dc.contributor.authorMasuda, N-
dc.contributor.authorPalacova, M-
dc.contributor.authorTrudeau, ME-
dc.contributor.authorMattson, J-
dc.contributor.authorYap, YS-
dc.contributor.authorV, MF-
dc.contributor.authorDe Laurentiis, M-
dc.contributor.authorYeh, YM-
dc.contributor.authorChang, HT-
dc.contributor.authorYau, T-
dc.contributor.authorWildiers, H-
dc.contributor.authorHaley, B-
dc.contributor.authorFagnani, D-
dc.contributor.authorLu, YS-
dc.contributor.authorCrown, J-
dc.contributor.authorLin, J-
dc.contributor.authorTakahashi, M-
dc.contributor.authorTakano, T-
dc.contributor.authorYamaguchi, M-
dc.contributor.authorFujii, T-
dc.contributor.authorYao, B-
dc.contributor.authorBebchuk, J-
dc.contributor.authorKeyvanjah, K-
dc.contributor.authorBryce, R-
dc.contributor.authorBrufsky, A-
dc.contributor.authorThe NALA Investigators-
dc.date.accessioned2020-10-22T08:17:12Z-
dc.date.available2020-10-22T08:17:12Z-
dc.date.issued2020-
dc.identifier.citationJournal of Clinical Oncology, 2020, v. 38 n. 27, p. 3138-3149-
dc.identifier.issn0732-183X-
dc.identifier.urihttp://hdl.handle.net/10722/289768-
dc.description.abstractPURPOSE: 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.-
dc.languageeng-
dc.publisherAmerican Society of Clinical Oncology. The Journal's web site is located at http://www.jco.org/-
dc.relation.ispartofJournal of Clinical Oncology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectabdominal infection-
dc.subjectabdominal pain-
dc.subjectacute kidney failure-
dc.subjectadult-
dc.subjectanemia-
dc.titleNeratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial-
dc.typeArticle-
dc.identifier.emailYau, T: tyaucc@hku.hk-
dc.identifier.authorityYau, T=rp01466-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1200/JCO.20.00147-
dc.identifier.pmid32678716-
dc.identifier.pmcidPMC7499616-
dc.identifier.scopuseid_2-s2.0-85088803559-
dc.identifier.hkuros316106-
dc.identifier.volume38-
dc.identifier.issue27-
dc.identifier.spage3138-
dc.identifier.epage3149-
dc.identifier.isiWOS:000574581200001-
dc.publisher.placeUnited States-
dc.identifier.issnl0732-183X-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats