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Title: Impact of prior (neo)adjuvant trastuzumab (NAT) exposure on the efficacy of HER2-targeted therapy for metastatic breast cancer.
Austin Authors: Kanjanapan, Yada;Lok, Sheau Wen;Gibbs, Peter;De Boer, Richard;Yeo, Belinda ;Greenberg, Sally;Barnett, Frances;Knott, Louise;Richardson, Gary;Wong, Rachel;Nottage, Michelle;Collins, Ian M;Torres, Javier;Lombard, Janine;Johns, Julie;Harold, Michael;Malik, Laeeq
Affiliation: Olivia Newton-John Cancer Wellness and Research Centre
Goulburn Valley Health, Shepparton, VIC, Australia
South Western Oncology, Warrnambool, VIC, Australia
Royal Brisbane Hospital, Brisbane, Australia
Eastern Health, Melbourne, Australia
Cabrini Institute, Melbourne, Australia
Royal Hobart Hospital, Hobart, Australia
Northern Health, Melbourne, Australia
Western Health, Melbourne, Australia
Calvary Mater Newcastle, Newcastle, Australia
Peter MacCallum Cancer Centre, Melbourne, Australia
Walter and Eliza Hall Institute, Melbourne, Australia
The Canberra Hospital, Canberra, Australia
Issue Date: Nov-2020 2020-08-10
Publication information: Breast Cancer Research and Treatment 2020; 184(1): 87-95
Abstract: Trastuzumab, pertuzumab, and docetaxel are the standard first-line therapy for HER2-positive (HER2+) metastatic breast cancer (MBC). However, only 10% of patients received neoadjuvant and/or adjuvant trastuzumab (NAT) in the registration trial (NCT00567190). In contemporary practice, the majority of recurrent HER2+ MBC patients had prior NAT. We explore any impact of prior therapy on the efficacy of dual HER2-targeted antibody with taxane therapy for metastatic disease. Utilising a prospective national registry, clinico-pathological, treatment, and outcome data for HER2+ MBC patients diagnosed between October 2006 and January 2019 were collected. Survival was estimated by the Kaplan-Meier method and compared among groups by log-rank test. Of 287 HER2+ MBC patients, 222 (77%) received first-line trastuzumab, pertuzumab, and taxane therapy. There were 130 (45%) with de novo MBC. Of the recurrent MBC patients 107/157 (68%) had received NAT. The median progression-free survival (PFS) among patients who received NAT was 15.8 months compared with 24.3 months without prior NAT (hazard ratio [HR] 1.45, 95% CI 1.05-2.03, p = 0.03). The median overall survival (OS) was 42.7 months in patients who had NAT, and was not reached in those who did not (HR 1.80, 95% CI 1.12-2.90, p = 0.02). However, when excluding de novo MBC patients, prior NAT exposure was no longer significantly associated with survival (p = 0.11). De novo MBC patients had the longest median PFS (25.2 months) and OS (91.2 months). Prior receipt of NAT was associated with inferior median PFS following first-line HER2-based therapy in the metastatic setting. However, prior NAT exposure did not significantly impact OS, supporting the efficacy of taxane, trastuzumab, pertuzumab combination for first-line HER2+ MBC regardless of prior NAT exposure. Patients with de novo MBC had the longest survival, suggesting stratification for synchronous versus metachronous disease in prospective clinical trials of MBC should be considered.
DOI: 10.1007/s10549-020-05825-w
ORCID: 0000-0002-9807-8695
PubMed URL: 32779037
Type: Journal Article
Subjects: De novo
Metastatic breast cancer
Appears in Collections:Journal articles

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