# Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study

Source: https://onco.cc/key-papers/paper-javle-mypathway-her2-biliary-lancet-oncol-2021/  
OnCo record `paper-javle-mypathway-her2-biliary-lancet-oncol-2021` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

39 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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: The Lancet Oncology
- Year: 2021
- DOI: 10.1016/s1470-2045(21)00336-3
- Authors: Javle M, Borad MJ, Azad NS, et al.
- 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.
- What it means: 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.

## Sources

- Javle et al., Lancet Oncol 2021: pertuzumab and trastuzumab in HER2-positive biliary tract cancer (MyPathway): https://doi.org/10.1016/s1470-2045(21)00336-3
- PubMed: https://pubmed.ncbi.nlm.nih.gov/34339623/
- ClinicalTrials.gov NCT02091141: https://clinicaltrials.gov/study/NCT02091141

## Connected records

- cancers: [Biliary tract cancer (all types)](https://onco.cc/cancers/biliary-tract-cancer/), [Biliary tract cancer (cholangiocarcinoma)](https://onco.cc/cancers/cholangiocarcinoma/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/)
- targets: [HER2](https://onco.cc/targets/her2/)
- drugs: [Pertuzumab](https://onco.cc/drugs/pertuzumab/), [Trastuzumab](https://onco.cc/drugs/trastuzumab/)
- companies: [Roche / Genentech](https://onco.cc/companies/roche-genentech/)
- trials: [MyPathway](https://onco.cc/trials/mypathway/)
- people: [Ghassan K. Abou-Alfa](https://onco.cc/people/ghassan-abou-alfa/)
- journals: [The Lancet Oncology](https://onco.cc/journals/lancet-oncology/)

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