{"entity":{"id":"paper-javle-mypathway-her2-biliary-lancet-oncol-2021","kind":"paper","name":"Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study","aka":[],"tldr":"Two HER2 antibodies together shrank tumours in about a quarter of 39 patients with HER2-positive bile duct or gallbladder cancer that had already been treated, with manageable side effects, prompting the later randomised HER2 trials.","summary":"MyPathway is a non-randomised, multicentre, open-label, phase 2a, multiple basket study of approved therapies in non-indicated tumours with actionable alterations. Patients aged 18 or older with previously treated metastatic biliary tract cancer with HER2 amplification, overexpression or both and ECOG performance status 0 to 2 were enrolled at 23 United States sites and received pertuzumab (840 mg loading, then 420 mg every 3 weeks) plus trastuzumab (8 mg/kg loading, then 6 mg/kg every 3 weeks). The primary endpoint was investigator-assessed objective response rate by RECIST 1.1.\n\n39 patients enrolled between October 2014 and May 2019 were evaluable at the March 2020 cut-off (median follow-up 8.1 months). Nine of 39 achieved a partial response (objective response rate 23%, 95% CI 11 to 39). Grade 3 to 4 treatment-emergent adverse events occurred in 18 (46%) of 39, most commonly raised alanine and aspartate aminotransferase (13% each); treatment-related grade 3 events in 3 (8%); no treatment-related serious adverse events, grade 4 events or deaths.","asOf":"2026-09-24","links":[{"label":"Javle et al., Lancet Oncol 2021: pertuzumab and trastuzumab in HER2-positive biliary tract cancer (MyPathway)","url":"https://doi.org/10.1016/s1470-2045(21)00336-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34339623/"},{"label":"ClinicalTrials.gov NCT02091141","url":"https://clinicaltrials.gov/study/NCT02091141"}],"tags":[],"related":[],"cancers":["gallbladder","biliary-tract-cancer","cholangiocarcinoma"],"sections":[],"technologies":[],"targets":["her2"],"drugs":["pertuzumab","trastuzumab"],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":[],"trials":["mypathway"],"people":["ghassan-abou-alfa"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/s1470-2045(21)00336-3","pmid":"34339623","authors":"Javle M, Borad MJ, Azad NS, et al.","paperType":"observational","findings":["Objective response rate 23% (9 of 39; 95% CI 11 to 39) with pertuzumab plus trastuzumab in previously treated HER2-positive biliary tract cancer.","Grade 3 to 4 treatment-emergent adverse events in 46%; treatment-related grade 3 in 8%; no treatment-related deaths.","HER2 positivity defined as amplification, overexpression or both."],"whatItMeans":"The first prospective evidence that HER2 blockade works in biliary cancer, which led to HERIZON-BTC-01 and the HER2 antibody-drug conjugate studies; the definition of HER2-positive here (amplification or overexpression) is looser than the later IHC 3+ label.","caveats":["Single-arm basket cohort of 39; no comparator.","Investigator-assessed responses."],"changedPractice":false,"participants":39},"route":"/key-papers/paper-javle-mypathway-her2-biliary-lancet-oncol-2021/","neighbours":{"cancer":[{"id":"biliary-tract-cancer","kind":"cancer","name":"Biliary tract cancer (all types)","route":"/cancers/biliary-tract-cancer/"},{"id":"cholangiocarcinoma","kind":"cancer","name":"Biliary tract cancer (cholangiocarcinoma)","route":"/cancers/cholangiocarcinoma/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"drug":[{"id":"pertuzumab","kind":"drug","name":"Pertuzumab","route":"/drugs/pertuzumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}],"company":[{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"trial":[{"id":"mypathway","kind":"trial","name":"MyPathway","route":"/trials/mypathway/"}],"person":[{"id":"ghassan-abou-alfa","kind":"person","name":"Ghassan K. Abou-Alfa","route":"/people/ghassan-abou-alfa/"}],"journal":[{"id":"lancet-oncology","kind":"journal","name":"The Lancet Oncology","route":"/journals/lancet-oncology/"}]}}