{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:24:27Z","timestamp":1793316267522,"version":"4.5.0"},"reference-count":15,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2022,9,1]]},"abstract":"\n Importance<\/jats:title>\n \n Addition of immune checkpoint inhibitors to anti-\n ERBB2<\/jats:italic>\n treatment has shown synergistic efficacy in preclinical studies and is thus worth investigating as a neoadjuvant treatment to maximize efficacy and to minimize toxic effects.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To determine if neoadjuvant atezolizumab, docetaxel, trastuzumab, and pertuzumab therapy for\n ERBB2<\/jats:italic>\n -positive early breast cancer warrants continuation to the next phase.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n This nonrandomized, open label, multicenter, phase 2 trial was conducted by the Korean Cancer Study Group and enrolled patients across 6 institutions in Korea from May 2019 to May 2020. Eligible patients were diagnosed with\n ERBB2<\/jats:italic>\n -positive breast cancer (primary tumor size &gt;2 cm or pathologically confirmed lymph node\u2013positive cancer, without distant metastases) with a clinical stage of II or III.\n <\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n \n Patients received 6 cycles of neoadjuvant pertuzumab (840 mg at first cycle, 420 mg during subsequent cycles), atezolizumab (1200 mg), docetaxel (75 mg\/m\n 2<\/jats:sup>\n ), and trastuzumab (600 mg via subcutaneous injection) every 3 weeks, followed by surgery. Patients with pathologic complete response (pCR) received 12 cycles of adjuvant atezolizumab, trastuzumab, and pertuzumab every 3 weeks after surgery. Patients without pCR were treated with 14 cycles of atezolizumab, 1200 mg, plus trastuzumab emtansine, 3.6 mg\/kg, every 3 weeks.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary end point was pCR rate, which was defined as the absence of invasive cancer cells in the primary tumor and regional lymph nodes (ypT0\/isN0). Secondary end points included clinical objective response rate, 3-year event-free survival rate according to pCR achievement, disease-free survival, overall survival, toxic effects, and quality-of-life outcomes.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n A total of 67 women (median [range] age, 52 [33-74] years) were enrolled. Hormone receptor expression was positive in 32 (48%) patients. Curative surgery was performed in 65 patients because 2 patients showed disease progression during neoadjuvant treatment and their tumors became unresectable. The overall pCR rate was 61% (41 of 67 patients). The pCR rate was higher in hormone receptor\u2013negative disease vs hormone receptor\u2013positive disease (27 of 35 [77%] patients vs 14 of 32 [44%] patients) and in programmed cell death 1\u2013positive expression vs programmed cell death 1\u2013negative expression (13 of 13 [100%] patients vs 28 of 53 [53%] patients). Grade 3 and 4 neutropenia and febrile neutropenia occurred in 8 (12%) patients and 5 (8%) patients, respectively. Grade 3 and 4 immune-related adverse events occurred in only 4 patients (grade 3 skin rash, encephalitis, hepatitis, and fever). No treatment-related death occurred during the neoadjuvant phase.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n In this nonrandomized clinical trial, treatment with the neoadjuvant atezolizumab, docetaxel, trastuzumab, and pertuzumab regimen in patients with stage II or III\n ERBB2<\/jats:italic>\n -positive breast cancer appears to have had an acceptable pCR rate and modest toxic effects. Further investigation of this immunotherapy combination in\n ERBB2<\/jats:italic>\n -positive early breast cancer is warranted.\n <\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT03881878<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaoncol.2022.2310","type":"journal-article","created":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T11:32:04Z","timestamp":1657193524000},"page":"1271","source":"Crossref","is-referenced-by-count":53,"title":["Response Rate and Safety of a Neoadjuvant Pertuzumab, Atezolizumab, Docetaxel, and Trastuzumab Regimen for Patients With\n ERBB2<\/i>\n -Positive Stage II\/III Breast Cancer"],"prefix":"10.1001","volume":"8","author":[{"given":"Hee Kyung","family":"Ahn","sequence":"first","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Hoon","family":"Sim","sequence":"additional","affiliation":[{"name":"Center for Breast Cancer, National Cancer Center, Goyang, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koung Jin","family":"Suh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Hwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Ho","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae-Won","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Hee","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heejung","family":"Chae","sequence":"additional","affiliation":[{"name":"Center for Breast Cancer, National Cancer Center, Goyang, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Hun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jee Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keun Seok","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Breast Cancer, National Cancer Center, Goyang, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Hyuk","family":"Sohn","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon-La","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seock-Ah","family":"Im","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Hae","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeon Hee","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"2","key":"coi220029r1","doi-asserted-by":"publisher","first-page":"e58","DOI":"10.1016\/S1470-2045(13)70477-7","article-title":"The immune system and response to HER2-targeted treatment in breast cancer.","volume":"15","author":"Bianchini","year":"2014","journal-title":"Lancet Oncol"},{"issue":"1","key":"coi220029r2","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/S1470-2045(17)30904-X","article-title":"Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy.","volume":"19","author":"Denkert","year":"2018","journal-title":"Lancet Oncol"},{"issue":"17","key":"coi220029r3","doi-asserted-by":"publisher","first-page":"5650","DOI":"10.1158\/1078-0432.CCR-04-0225","article-title":"Pilot study of the mechanism of action of preoperative trastuzumab in patients with primary operable breast tumors overexpressing HER2.","volume":"10","author":"Gennari","year":"2004","journal-title":"Clin Cancer Res"},{"issue":"315","key":"coi220029r4","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aac4925","article-title":"Trastuzumab emtansine (T-DM1) renders HER2+ breast cancer highly susceptible to CTLA-4\/PD-1 blockade.","volume":"7","author":"M\u00fcller","year":"2015","journal-title":"Sci Transl Med"},{"issue":"17","key":"coi220029r5","doi-asserted-by":"publisher","first-page":"7142","DOI":"10.1073\/pnas.1016569108","article-title":"Anti-ErbB-2 mAb therapy requires type I and II interferons and synergizes with anti-PD-1 or anti-CD137 mAb therapy.","volume":"108","author":"Stagg","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"coi220029r6","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/S1470-2045(11)70336-9","article-title":"Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial.","volume":"13","author":"Gianni","year":"2012","journal-title":"Lancet Oncol"},{"issue":"1","key":"coi220029r7","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/S1470-2045(17)30716-7","article-title":"Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial.","volume":"19","author":"Hurvitz","year":"2018","journal-title":"Lancet Oncol"},{"issue":"9","key":"coi220029r8","doi-asserted-by":"publisher","first-page":"2278","DOI":"10.1093\/annonc\/mdt182","article-title":"Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA).","volume":"24","author":"Schneeweiss","year":"2013","journal-title":"Ann Oncol"},{"key":"coi220029r9","doi-asserted-by":"publisher","DOI":"10.4143\/crt.2021.901","article-title":"Real world evidence of neoadjuvant docetaxel\/carboplatin\/trastuzumab\/pertuzumab (TCHP) in patients with HER2-positive early or locally advanced breast cancer: a single-institutional clinical experience.","author":"Kim","year":"2022","journal-title":"Cancer Res Treat"},{"issue":"10","key":"coi220029r10","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1016\/S1470-2045(20)30465-4","article-title":"Trastuzumab emtansine plus atezolizumab versus trastuzumab emtansine plus placebo in previously treated, HER2-positive advanced breast cancer (KATE2): a phase 2, multicentre, randomised, double-blind trial.","volume":"21","author":"Emens","year":"2020","journal-title":"Lancet Oncol"},{"issue":"8","key":"coi220029r11","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1016\/j.annonc.2021.05.800","article-title":"VP6-2021: IMpassion050: a phase III study of neoadjuvant atezolizumab?+?pertuzumab?+?trastuzumab?+?chemotherapy (neoadj A?+PH?+?CT) in high-risk, HER2-positive early breast cancer (EBC).","volume":"32","author":"Huober","year":"2021","journal-title":"Ann Oncol"},{"issue":"3","key":"coi220029r12","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/S1470-2045(18)30812-X","article-title":"Pembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b-2 trial.","volume":"20","author":"Loi","year":"2019","journal-title":"Lancet Oncol"},{"key":"coi220029r13","doi-asserted-by":"publisher","first-page":"PD3","DOI":"10.1158\/1538-7445.SABCS20-PD3-05","article-title":"Abstract PD3-05: the DAPHNE trial: a feasibility study of chemotherapy de-escalation based on response to neoadjuvant paclitaxel-HP (THP) in HER2-positive breast cancer.","volume":"81","author":"Waks","year":"2021","journal-title":"Cancer Res"},{"key":"coi220029r14","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1200\/JCO.2021.39.15_suppl.506","article-title":"Durvalumab improves long-term outcome in TNBC: results from the phase II randomized GeparNUEVO study investigating neodjuvant durvalumab in addition to an anthracycline\/taxane based neoadjuvant chemotherapy in early triple-negative breast cancer (TNBC).","volume":"39","author":"Loibl","year":"2021","journal-title":"J Clin Oncol"},{"issue":"6","key":"coi220029r15","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1056\/NEJMoa2112651","article-title":"Event-free survival with pembrolizumab in early triple-negative breast cancer.","volume":"386","author":"Schmid","year":"2022","journal-title":"N Engl J Med"}],"container-title":["JAMA Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/articlepdf\/2794150\/jamaoncology_ahn_2022_oi_220029_1663179793.92877.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T11:07:58Z","timestamp":1663240078000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/fullarticle\/2794150"}},"subtitle":["The Neo-PATH Phase 2 Nonrandomized Clinical Trial"],"short-title":[],"issued":{"date-parts":[[2022,9,1]]},"references-count":15,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2022,9,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaoncol.2022.2310","relation":{},"ISSN":["2374-2437"],"issn-type":[{"value":"2374-2437","type":"print"}],"subject":[],"published":{"date-parts":[[2022,9,1]]}}}