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.
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.
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.
Shares Pertuzumab, Trastuzumab, Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma).
Shares Ghassan K. Abou-Alfa, The Lancet Oncology, Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma).
Shares Trastuzumab, Biliary tract cancer (all types), HER2, Biliary tract cancer (cholangiocarcinoma).
Shares Ghassan K. Abou-Alfa, Biliary tract cancer (all types), HER2, Biliary tract cancer (cholangiocarcinoma).
Shares Trastuzumab, Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer.
Shares Trastuzumab, Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer.
Shares MyPathway, The Lancet Oncology.
Shares Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer.