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Article: Analysis of the pan-Asian subgroup of patients in the NALA Trial: a randomized phase III NALA Trial comparing neratinib+capecitabine (N+C) vs lapatinib+capecitabine (L+C) in patients with HER2+metastatic breast cancer (mBC) previously treated with two or more HER2-directed regimens

TitleAnalysis of the pan-Asian subgroup of patients in the NALA Trial: a randomized phase III NALA Trial comparing neratinib+capecitabine (N+C) vs lapatinib+capecitabine (L+C) in patients with HER2+metastatic breast cancer (mBC) previously treated with two or more HER2-directed regimens
Authors
KeywordsNeratinib
Tyrosine kinase inhibitor
HER2-positive breast cancer
Brain metastases
CNS metastases
Lapatinib
Issue Date2021
PublisherSpringer New York LLC. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0167-6806
Citation
Breast Cancer Research and Treatment, 2021, v. 189 n. 3, p. 665-676 How to Cite?
AbstractPurpose: Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated systemic efficacy and intracranial activity in various stages of HER2+breast cancer. NALA was a phase III randomized trial that assessed the efficacy and safety of neratinib+capecitabine (N+C) against lapatinib+capecitabine (L+C) in HER2+ metastatic breast cancer (mBC) patients who had received ≥ 2 HER2-directed regimens. Descriptive analysis results of the Asian subgroup in the NALA study are reported herein. Methods: 621 centrally assessed HER2+ mBC patients were enrolled, 202 of whom were Asian. Those with stable, asymptomatic brain metastases (BM) were eligible for study entry. Patients were randomized 1:1 to N (240 mg qd) + C (750 mg/m2 bid, day 1–14) with loperamide prophylaxis or to L (1250 mg qd) + C (1000 mg/m2 bid, day 1–14) in 21-day cycles. Co-primary endpoints were centrally assessed progression-free survival (PFS) and overall survival (OS). Secondary endpoints included time to intervention for central nervous system (CNS) disease, objective response rate, duration of response (DoR), clinical benefit rate, and safety. Results: 104 and 98 Asian patients were randomly assigned to receive N+C or L+C, respectively. Median PFS of N+C and L+C was 7.0 and 5.4 months (P = 0.0011), respectively. Overall cumulative incidence of intervention for CNS disease was lower with N+C (27.9 versus 33.8%; P = 0.039). Both median OS (23.8 versus 18.7 months; P = 0.185) and DoR (11.1 versus 4.2 months; P < 0.0001) were extended with N+C, compared to L+C. The incidences of grade 3/4 treatment emergent adverse events (TEAEs) and TEAEs leading to treatment discontinuation were mostly comparable between the two arms. Diarrhea and palmar-plantar erythrodysesthesia were the most frequent TEAEs in both arms, similar to the overall population in incidence and severity. Conclusion: Consistent with the efficacy profile observed in the overall study population, Asian patients with HER2+ mBC, who had received ≥ 2 HER2-directed regimens, may also benefit from N+C. No new safety signals were noted. Clinical trial registration: NCT01808573
Persistent Identifierhttp://hdl.handle.net/10722/304989
ISSN
2021 Impact Factor: 4.624
2020 SCImago Journal Rankings: 1.908
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorDai, MS-
dc.contributor.authorFeng, YH-
dc.contributor.authorChen, SW-
dc.contributor.authorMasuda, N-
dc.contributor.authorYau, T-
dc.contributor.authorChen, ST-
dc.contributor.authorLu, YS-
dc.contributor.authorYap, YS-
dc.contributor.authorAng, PCS-
dc.contributor.authorChu, SC-
dc.contributor.authorKwong, A-
dc.contributor.authorLee, KS-
dc.contributor.authorOw, S-
dc.contributor.authorKim, SB-
dc.contributor.authorLin, J-
dc.contributor.authorChung, HC-
dc.contributor.authorNgan, R-
dc.contributor.authorKok, VC-
dc.contributor.authorRau, KM-
dc.contributor.authorSangai, T-
dc.contributor.authorNg, TY-
dc.contributor.authorTseng, LM-
dc.contributor.authorBryce, R-
dc.contributor.authorBebchuk, J-
dc.contributor.authorChen, MC-
dc.contributor.authorHou, MF-
dc.date.accessioned2021-10-05T02:38:08Z-
dc.date.available2021-10-05T02:38:08Z-
dc.date.issued2021-
dc.identifier.citationBreast Cancer Research and Treatment, 2021, v. 189 n. 3, p. 665-676-
dc.identifier.issn0167-6806-
dc.identifier.urihttp://hdl.handle.net/10722/304989-
dc.description.abstractPurpose: Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated systemic efficacy and intracranial activity in various stages of HER2+breast cancer. NALA was a phase III randomized trial that assessed the efficacy and safety of neratinib+capecitabine (N+C) against lapatinib+capecitabine (L+C) in HER2+ metastatic breast cancer (mBC) patients who had received ≥ 2 HER2-directed regimens. Descriptive analysis results of the Asian subgroup in the NALA study are reported herein. Methods: 621 centrally assessed HER2+ mBC patients were enrolled, 202 of whom were Asian. Those with stable, asymptomatic brain metastases (BM) were eligible for study entry. Patients were randomized 1:1 to N (240 mg qd) + C (750 mg/m2 bid, day 1–14) with loperamide prophylaxis or to L (1250 mg qd) + C (1000 mg/m2 bid, day 1–14) in 21-day cycles. Co-primary endpoints were centrally assessed progression-free survival (PFS) and overall survival (OS). Secondary endpoints included time to intervention for central nervous system (CNS) disease, objective response rate, duration of response (DoR), clinical benefit rate, and safety. Results: 104 and 98 Asian patients were randomly assigned to receive N+C or L+C, respectively. Median PFS of N+C and L+C was 7.0 and 5.4 months (P = 0.0011), respectively. Overall cumulative incidence of intervention for CNS disease was lower with N+C (27.9 versus 33.8%; P = 0.039). Both median OS (23.8 versus 18.7 months; P = 0.185) and DoR (11.1 versus 4.2 months; P < 0.0001) were extended with N+C, compared to L+C. The incidences of grade 3/4 treatment emergent adverse events (TEAEs) and TEAEs leading to treatment discontinuation were mostly comparable between the two arms. Diarrhea and palmar-plantar erythrodysesthesia were the most frequent TEAEs in both arms, similar to the overall population in incidence and severity. Conclusion: Consistent with the efficacy profile observed in the overall study population, Asian patients with HER2+ mBC, who had received ≥ 2 HER2-directed regimens, may also benefit from N+C. No new safety signals were noted. Clinical trial registration: NCT01808573-
dc.languageeng-
dc.publisherSpringer New York LLC. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0167-6806-
dc.relation.ispartofBreast Cancer Research and Treatment-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectNeratinib-
dc.subjectTyrosine kinase inhibitor-
dc.subjectHER2-positive breast cancer-
dc.subjectBrain metastases-
dc.subjectCNS metastases-
dc.subjectLapatinib-
dc.titleAnalysis of the pan-Asian subgroup of patients in the NALA Trial: a randomized phase III NALA Trial comparing neratinib+capecitabine (N+C) vs lapatinib+capecitabine (L+C) in patients with HER2+metastatic breast cancer (mBC) previously treated with two or more HER2-directed regimens-
dc.typeArticle-
dc.identifier.emailYau, T: tyaucc@hku.hk-
dc.identifier.emailKwong, A: avakwong@hku.hk-
dc.identifier.emailNgan, R: rkcngan@hku.hk-
dc.identifier.authorityYau, T=rp01466-
dc.identifier.authorityKwong, A=rp01734-
dc.identifier.authorityNgan, R=rp02371-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1007/s10549-021-06313-5-
dc.identifier.pmid34553296-
dc.identifier.pmcidPMC8505315-
dc.identifier.scopuseid_2-s2.0-85115321616-
dc.identifier.hkuros326273-
dc.identifier.volume189-
dc.identifier.issue3-
dc.identifier.spage665-
dc.identifier.epage676-
dc.identifier.isiWOS:000698329600001-
dc.publisher.placeUnited States-

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