{"entity":{"id":"pertuzumab","kind":"drug","name":"Pertuzumab","aka":[],"tldr":"A second HER2 antibody that binds a different spot from trastuzumab, blocking HER2 from pairing with HER3; together they extended survival by 16 months in CLEOPATRA.","summary":"Binds HER2 extracellular domain II, preventing HER2-HER3 heterodimerisation. Approved with trastuzumab and docetaxel in first-line metastatic disease (2012), neoadjuvant (2013, first pCR-based accelerated approval), and adjuvant node-positive disease (2017, APHINITY). Phesgo (2020) delivers both antibodies subcutaneously in minutes. Being partnered with T-DXd in first line (DESTINY-Breast09) and tucatinib in maintenance (HER2CLIMB-05).","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Pertuzumab","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Pertuzumab"}],"tags":[],"related":["her2-ish-amplified"],"cancers":["breast-her2-positive","her2-positive-early-breast-cancer","gallbladder","cholangiocarcinoma","colorectal","biliary-tract-cancer"],"sections":[],"technologies":["monoclonal-antibody"],"targets":["her2","her3"],"drugs":[],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":[],"trials":["cleopatra","aphinity","destiny-breast09","her2climb-05","phergain","nct07518173","nct07196774","nct06891833","nct05593094","nct06445400","nct07102381","nct05802225","nct07294508","nct06057610","nct04208178","nct06771622","nct04538742","nct06178159","nct00781612","nct06686394","nct02320435","nct05150691","nct07140393","nct04514419","mypathway","determine-arm04"],"people":[],"bottlenecks":[],"keyPapers":["paper-nakamura-triumph-ctdna-pertuzumab-trastuzumab-her2-colorectal-nat-med-2021","paper-javle-mypathway-her2-biliary-lancet-oncol-2021"],"journals":[],"dependsOn":[],"notes":["Biliary tract cancer: with trastuzumab in the MyPathway basket, 9 of 39 patients with HER2-amplified or overexpressing metastatic biliary tract cancer responded (23 percent, 95 percent confidence interval 11 to 39); the UK DETERMINE platform (Cancer Research UK) offers the same pair to HER2-amplified rare cancers including gallbladder cancer at 27 NHS sites.","Colorectal cancer biomarkers: TRIUMPH enrolled on HER2 amplification confirmed in tissue or in circulating tumour DNA and gave confirmed responses in 30% of 27 tissue-positive and 28% of 25 ctDNA-positive patients, against 0% in a matched real-world salvage population; concurrent oncogenic RAS alterations in plasma predicted poor response (Nakamura 2021)."],"brand":"Perjeta; Phesgo (with trastuzumab, subcutaneous)","modality":"Monoclonal antibody (anti-HER2, dimerisation domain)","mechanism":"Anti-HER2 IgG1 against subdomain II; blocks ligand-dependent HER2-HER3 signalling; ADCC.","approvals":[{"region":"US","year":2012,"indication":"First-line HER2+ metastatic breast cancer with trastuzumab and docetaxel"},{"region":"US","year":2013,"indication":"Neoadjuvant HER2+ early breast cancer (accelerated; first pCR-based approval)"},{"region":"US","year":2017,"indication":"Adjuvant HER2+ early breast cancer at high risk of recurrence"},{"region":"US","year":2020,"indication":"Phesgo subcutaneous fixed-dose combination with trastuzumab"}],"mechanismSteps":["HER3, activated by neuregulin, seeks HER2 as a dimer partner","Pertuzumab occupies HER2 domain II, the dimerisation arm","HER2-HER3 pairs cannot form; PI3K signalling drops","Trastuzumab meanwhile blocks domain IV and recruits NK cells","Complementary blockade deepens response"],"dosing":{"route":"Intravenous (or subcutaneous as Phesgo)","schedule":"840 mg loading then 420 mg every 3 weeks; Phesgo 1200/600 mg loading then 600/600 mg SC every 3 weeks","monitoring":"LVEF at baseline and every 3 months","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125409s128lbl.pdf"},"toxicity":[{"event":"Diarrhoea","anyGradePct":67,"grade3PlusPct":8},{"event":"Rash","anyGradePct":34},{"event":"Left ventricular dysfunction","anyGradePct":5,"grade3PlusPct":1.2},{"event":"Febrile neutropenia (with docetaxel)","grade3PlusPct":14}],"access":[],"regulatoryEvents":[{"date":"2012-06-08","type":"approval","region":"US","note":"First-line metastatic (CLEOPATRA)"},{"date":"2013-09-30","type":"accelerated-approval","region":"US","note":"Neoadjuvant accelerated approval on pCR","indication":"In combination with trastuzumab and docetaxel for neoadjuvant treatment of HER2-positive locally advanced inflammatory or early-stage breast cancer (either greater than 2 cm in diameter or node-positive) as part of a complete treatment regimen for early early breast cancer"},{"date":"2017-12-20","type":"conversion","region":"US","note":"Adjuvant (APHINITY)","indication":"In combination with trastuzumab and docetaxel for neoadjuvant treatment of HER2-positive locally advanced inflammatory or early-stage breast cancer (either greater than 2 cm in diameter or node-positive) as part of a complete treatment regimen for early early breast cancer"},{"date":"2020-06-29","type":"approval","region":"US","note":"Phesgo SC"},{"date":"2026-06-24","type":"approval","region":"US","note":"FDA approves palbociclib with trastuzumab, with or without pertuzumab, and endocrine therapy for the maintenance treatment of HR-positive, HER2-positive metastatic breast cancer","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-palbociclib-trastuzumab-or-without-pertuzumab-and-endocrine-therapy-maintenance"}]},"route":"/drugs/pertuzumab/","neighbours":{"biomarker":[{"id":"her2-ihc-3-plus","kind":"biomarker","name":"HER2 IHC 3+ (HER2-positive by immunohistochemistry)","route":"/biomarkers/her2-ihc-3-plus/"},{"id":"her2-ish-amplified","kind":"biomarker","name":"HER2 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