{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:08:21Z","timestamp":1792084101461,"version":"4.4.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Provincial Natural Science Foundation of China","award":["2025JJ80824"],"award-info":[{"award-number":["2025JJ80824"]}]},{"name":"Provincial Natural Science Foundation of China","award":["2024JJ6289"],"award-info":[{"award-number":["2024JJ6289"]}]},{"name":"Provincial Natural Science Foundation of China","award":["2023JJ60464"],"award-info":[{"award-number":["2023JJ60464"]}]},{"name":"Provincial Natural Science Foundation of China","award":["2023JJ60334"],"award-info":[{"award-number":["2023JJ60334"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Importance<\/jats:title>\n                  <jats:p>THP (trastuzumab + paclitaxel + pertuzumab) and THPy (trastuzumab + paclitaxel + pyrotinib) are widely used as first-line regimens for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) in China. However, direct comparative data on their efficacy and safety remain scarce.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To evaluate and compare the clinical outcomes of THPy and THP in the first-line treatment of HER2-positive MBC to guide clinical decision-making.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Real-world, multicenter retrospective study conducted from 2020 to 2024.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>Five large breast cancer centers in China.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>A total of 145 patients with HER2-positive MBC were included before propensity score matching (PSM). After PSM, 76 patients (38 in each group) were analyzed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Intervention(s) or Exposure(s)<\/jats:title>\n                  <jats:p>Patients received either THP (trastuzumab + paclitaxel + pertuzumab) or THPy (trastuzumab + paclitaxel + pyrotinib) as first-line treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome(s) and Measure(s)<\/jats:title>\n                  <jats:p>The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate, and safety profile.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Before PSM, 145 patients were included, with the median follow-up of 9.4\u2009months. The ORR was significantly higher in the THPy group (75.0%) compared to the THP group (56.8%; P\u2009=\u2009.023). Median PFS showed a trend favoring THPy (19.80\u2009months vs 15.57\u2009months; Log-rank P\u2009=\u2009.343). After PSM, 76 patients were matched, with the median PFS of 24.33\u2009months versus 14.50\u2009months for THPy and THP groups, respectively. Though the difference in PFS was not statistically significant (Log-rank P\u2009=\u2009.309), THPy demonstrated a higher ORR compared to THP (78.9% vs 57.9%; P\u2009=\u2009.048). Further subgroup analysis revealed greater benefits of THPy, particularly in patients with prior neoadjuvant therapy (hazard ratio [HR] = 0.261; 95% CI: 0.072-0.940). Regarding safety, THPy was associated with a higher incidence of grade 3\/4 diarrhea (26.6% vs 3.1%) as well as increased rates of neutropenia, anemia, alanine aminotransferase elevation, fatigue, and peripheral neuropathy compared to THP.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion and Relevance<\/jats:title>\n                  <jats:p>Both THP and THPy are effective first-line options for HER2-positive MBC. While THPy demonstrates a higher ORR and a trend toward longer PFS, it also carries a higher incidence of adverse events, particularly diarrhea. These findings offer preliminary insights that may help inform treatment decisions, pending further validation in prospective studies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyaf277","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T16:20:22Z","timestamp":1757434822000},"source":"Crossref","is-referenced-by-count":5,"title":["Pyrotinib versus pertuzumab with trastuzumab and taxane in HER2-positive metastatic breast cancer: a Chinese multicenter real-world study"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3692-2272","authenticated-orcid":false,"given":"Binliang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital\/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University , Changsha 410013,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongbi","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University , Wuhan 430071,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital\/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University , Changsha 410013,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Thyroid Breast Surgery, The Second Affiliated Hospital, Hengyang Medical School, University of South China , Hengyang 421009,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronghua","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Oncology, Changde Hospital, Xiangya School of Medicine, Central South University , Changde 415000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe-Yu","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital\/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University , Changsha 410013,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital\/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University , Changsha 410013,","place":["China"]},{"name":"Department of Oncology, Hunan Institute of Schistosomiasis Control (The Third People\u2019s Hospital of Hunan Province) , Yueyang 414000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxin","family":"Li","sequence":"additional","affiliation":[{"name":"Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University and Affiliated Cancer Hospital of Qinghai University , Xining 810000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiuda","family":"Zhao","sequence":"additional","affiliation":[{"name":"Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University and Affiliated Cancer Hospital of Qinghai University , Xining 810000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Changde Hospital, Xiangya School of Medicine, Central South University , Changde 415000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1233-6081","authenticated-orcid":false,"given":"Quchang","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital\/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University , Changsha 410013,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"key":"2025100520021108300_oyaf277-B1","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.breast.2019.12.010","article-title":"Longitudinal HER2 amplification tracked in circulating tumor DNA for therapeutic effect monitoring and prognostic evaluation in patients with breast cancer","volume":"49","author":"Guan","year":"2020","journal-title":"Breast"},{"key":"2025100520021108300_oyaf277-B2","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1634\/theoncologist.2008-0230","article-title":"The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine","volume":"14","author":"Ross","year":"2009","journal-title":"Oncologist"},{"key":"2025100520021108300_oyaf277-B3","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1007\/s11864-023-01137-5","article-title":"Anti-HER2 drugs for the treatment of advanced HER2 positive breast cancer","volume":"24","author":"Stanowicka-Grada","year":"2023","journal-title":"Curr Treat Options Oncol"},{"key":"2025100520021108300_oyaf277-B4","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/S1470-2045(19)30863-0","article-title":"Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (cleopatra): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study","volume":"21","author":"Swain","year":"2020","journal-title":"Lancet Oncol"},{"key":"2025100520021108300_oyaf277-B5","doi-asserted-by":"publisher","first-page":"5212","DOI":"10.1158\/1078-0432.CCR-18-4173","article-title":"Safety, efficacy, and biomarker analysis of pyrotinib in combination with capecitabine in her2-positive metastatic breast cancer patients: a phase I clinical trial","volume":"25","author":"Li","year":"2019","journal-title":"Clin Cancer Res"},{"key":"2025100520021108300_oyaf277-B6","doi-asserted-by":"publisher","first-page":"e76065","DOI":"10.1136\/bmj-2023-076065","article-title":"Pyrotinib versus placebo in combination with trastuzumab and docetaxel as first line treatment in patients with HER2 positive metastatic breast cancer (PHILA): randomised, double blind, multicentre, phase 3 trial","volume":"383","author":"Ma","year":"2023","journal-title":"Bmj"},{"key":"2025100520021108300_oyaf277-B7","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/S1470-2045(20)30702-6","article-title":"Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (phoebe): a multicentre, open-label, randomised, controlled, phase 3 trial","volume":"22","author":"Xu","year":"2021","journal-title":"Lancet Oncol"},{"key":"2025100520021108300_oyaf277-B8","doi-asserted-by":"crossref","first-page":"2610","DOI":"10.1200\/JCO.19.00108","article-title":"Pyrotinib or lapatinib combined with capecitabine in HER2\u2013positive metastatic breast cancer with prior taxanes, anthracyclines, and\/or trastuzumab: a randomized, phase ii study","volume":"37","author":"Ma","year":"2019","journal-title":"J Clin Oncol"},{"key":"2025100520021108300_oyaf277-B9","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1016\/S1470-2045(14)70320-1","article-title":"Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response","volume":"15","author":"de Azambuja","year":"2014","journal-title":"Lancet Oncol"},{"key":"2025100520021108300_oyaf277-B10","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1186\/s12916-022-02708-3","article-title":"Neoadjuvant pyrotinib, trastuzumab, and docetaxel for HER2-positive breast cancer (PHEDRA): a double-blind, randomized phase 3 trial","volume":"20","author":"Wu","year":"2022","journal-title":"BMC Med"},{"key":"2025100520021108300_oyaf277-B11","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1001\/jamaoncol.2022.5610","article-title":"Tucatinib vs placebo, both in combination with trastuzumab and capecitabine, for previously treated ERBB2 (HER2)-positive metastatic breast cancer in patients with brain metastases: updated exploratory analysis of the HER2CLIMB randomized clinical trial","volume":"9","author":"Lin","year":"2023","journal-title":"Jama Oncol"},{"key":"2025100520021108300_oyaf277-B12","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur J Cancer"},{"key":"2025100520021108300_oyaf277-B13","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1016\/j.annonc.2021.06.024","article-title":"Final results from the peruse study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication","volume":"32","author":"Miles","year":"2021","journal-title":"Ann Oncol"},{"key":"2025100520021108300_oyaf277-B14","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/s41523-021-00274-0","article-title":"Neratinib plus trastuzumab is superior to pertuzumab plus trastuzumab in HER2-positive breast cancer xenograft models","volume":"7","author":"Veeraraghavan","year":"2021","journal-title":"NPJ Breast Cancer"},{"key":"2025100520021108300_oyaf277-B15","doi-asserted-by":"publisher","first-page":"105379","DOI":"10.1016\/j.ebiom.2024.105379","article-title":"Pyrotinib and trastuzumab combination treatment synergistically overcomes HER2 dependency in HER2-positive breast cancer: insights from the PHILA trial","volume":"109","author":"Liu","year":"2024","journal-title":"EBioMedicine"},{"key":"2025100520021108300_oyaf277-B16","doi-asserted-by":"publisher","first-page":"1871","DOI":"10.1158\/0008-5472.CAN-10-1872","article-title":"Trastuzumab has preferential activity against breast cancers driven by HER2 homodimers","volume":"71","author":"Ghosh","year":"2011","journal-title":"Cancer Res"},{"key":"2025100520021108300_oyaf277-B17","doi-asserted-by":"publisher","first-page":"124","DOI":"10.21147\/j.issn.1000-9604.2024.02.03","article-title":"Pyrotinib is effective in both trastuzumab-sensitive and primary resistant HER2-positive breast tumors","volume":"36","author":"Zhang","year":"2024","journal-title":"Chin J Cancer Res"},{"key":"2025100520021108300_oyaf277-B18","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13091446","article-title":"Brain metastasis treatment: the place of tyrosine kinase inhibitors and how to facilitate their diffusion across the blood-brain barrier","volume":"13","author":"Angeli","year":"2021","journal-title":"Pharmaceutics"},{"key":"2025100520021108300_oyaf277-B19","doi-asserted-by":"publisher","first-page":"1325540","DOI":"10.3389\/fendo.2023.1325540","article-title":"Comparing pyrotinib with trastuzumab and pertuzumab with trastuzumab for HER2-positive metastatic breast cancer: a retrospective, multicenter analysis","volume":"14","author":"You","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2025100520021108300_oyaf277-B20","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/s00432-023-05530-3","article-title":"Efficacy and safety of first-line therapy in patients with HER2-positive advanced breast cancer: a network meta-analysis of randomized controlled trials","volume":"150","author":"Wang","year":"2024","journal-title":"J Cancer Res Clin Oncol"},{"key":"2025100520021108300_oyaf277-B21","doi-asserted-by":"publisher","volume-title":"Cancer Innov","author":"Efficacy and safety of first","DOI":"10.1002\/cai2.126"},{"key":"2025100520021108300_oyaf277-B22","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1038\/s41572-019-0111-2","article-title":"Breast cancer","volume":"5","author":"Harbeck","year":"2019","journal-title":"Nat Rev Dis Primers"},{"key":"2025100520021108300_oyaf277-B23","doi-asserted-by":"publisher","first-page":"8314","DOI":"10.1038\/s41467-023-44140-y","article-title":"Pyrotinib plus docetaxel as first-line treatment for HER2-positive metastatic breast cancer: the PANDORA phase II trial","volume":"14","author":"Zheng","year":"2023","journal-title":"Nat Commun"},{"key":"2025100520021108300_oyaf277-B24","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1056\/NEJMoa1914609","article-title":"Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer","volume":"382","author":"Murthy","year":"2020","journal-title":"N Engl J Med"},{"key":"2025100520021108300_oyaf277-B25","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/S1470-2045(21)00716-6","article-title":"Pyrotinib plus capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases (permeate): a multicentre, single-arm, two-\u00adcohort, phase 2 trial","volume":"23","author":"Yan","year":"2022","journal-title":"Lancet Oncol"},{"key":"2025100520021108300_oyaf277-B26","doi-asserted-by":"publisher","first-page":"e198","DOI":"10.1093\/oncolo\/oyad228","article-title":"Long-term outcome analysis of pyrotinib in patients with HER2-positive metastatic breast cancer and brain metastasis: a real-world study","volume":"29","author":"Liang","year":"2024","journal-title":"Oncologist"},{"key":"2025100520021108300_oyaf277-B27","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.annonc.2023.12.001","article-title":"Trastuzumab deruxtecan in previously treated patients with HER2-positive metastatic breast cancer: updated survival results from a phase II trial (DESTINY-Breast01)","volume":"35","author":"Saura","year":"2024","journal-title":"Ann Oncol"},{"key":"2025100520021108300_oyaf277-B28","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1016\/S0140-6736(23)00725-0","article-title":"Trastuzumab deruxtecan versus treatment of physician\u2019s choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-\u00adlabel, multicentre, phase 3 trial","volume":"401","author":"Andr\u00e9","year":"2023","journal-title":"Lancet"},{"key":"2025100520021108300_oyaf277-B29","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/S0140-6736(22)02420-5","article-title":"Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial","volume":"401","author":"Hurvitz","year":"2023","journal-title":"Lancet"},{"key":"2025100520021108300_oyaf277-B30","doi-asserted-by":"publisher","first-page":"329","DOI":"10.3747\/co.21.2241","article-title":"Management of diarrhea induced by epidermal growth factor receptor tyrosine kinase inhibitors","volume":"21","author":"Hirsh","year":"2014","journal-title":"Curr Oncol"}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/oncolo\/advance-article-pdf\/doi\/10.1093\/oncolo\/oyaf277\/64232129\/oyaf277.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/30\/10\/oyaf277\/64232129\/oyaf277.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/30\/10\/oyaf277\/64232129\/oyaf277.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:02:21Z","timestamp":1759708941000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/doi\/10.1093\/oncolo\/oyaf277\/8250114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,9]]},"references-count":30,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10,1]]}},"URL":"https:\/\/doi.org\/10.1093\/oncolo\/oyaf277","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,10]]},"published":{"date-parts":[[2025,9,9]]},"article-number":"oyaf277"}}