Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label,
Milind Javle1, Mitesh J Borad2, Nilofer S Azad3
1Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Background:
Systemic therapies for metastatic biliary tract cancers are few, and patients have a median overall survival of less than 1 year. MyPathway evaluates the activity of US Food and Drug Administration-approved therapies in non-indicated tumours with potentially actionable molecular alterations. In this study, we present an analysis of patients with metastatic biliary tract cancers with HER2 amplification, overexpression, or both treated with a dual anti-HER2 regimen, pertuzumab plus trastuzumab, from MyPathway.
Methods:
MyPathway is a non-randomised, multicentre, open-label, phase 2a, multiple basket study. Patients aged 18 years and older with previously treated metastatic biliary tract cancers with HER2 amplification, HER2 overexpression, or both and an Eastern Cooperative Oncology Group performance status of 0-2 were enrolled from 23 study sites in the USA and received intravenous pertuzumab (840 mg loading dose, then 420 mg every 3 weeks) plus trastuzumab (8 mg/kg loading dose, then 6 mg/kg every 3 weeks). The primary endpoint was investigator-assessed objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The primary outcome and adverse events were analysed in all patients who received at least one dose of pertuzumab and trastuzumab. This trial is registered with ClinicalTrials.gov, NCT02091141, and is ongoing.
Findings:
39 patients enrolled in the MyPathway HER2 biliary tract cancer cohort between Oct 28, 2014, and May 29, 2019, were evaluable for anti-tumour activity by the March 10, 2020, data cutoff date. Median follow-up was 8·1 months (IQR 2·7-15·7). Nine of 39 patients achieved a partial response (objective response rate 23% [95% CI 11-39]). Grade 3-4 treatment-emergent adverse events were reported in 18 (46%) of 39 patients, most commonly increased alanine aminotransferase and increased aspartate aminotransferase (each five [13%] of 39). Treatment-related grade 3 adverse events were reported in three (8%) of 39 patients, including increased alanine aminotransferase, aspartate aminotransferase, blood alkaline phosphatase, and blood bilirubin. Serious treatment-emergent adverse events were observed in ten (26%) of 39 patients, of which only abdominal pain occurred in more than one patient (two [5%] of 39). There were no treatment-related serious adverse events, treatment-related grade 4 events, or deaths.
Interpretation:
Treatment was well tolerated in patients with previously treated HER2-positive metastatic biliary tract cancer. The response rate is promising for the initiation of randomised, controlled trials of pertuzumab plus trastuzumab in this patient population.
Funding:
F Hoffmann-La Roche-Genentech.
Insights
Dual anti-HER2 therapy with pertuzumab and trastuzumab showed a 23% response rate in patients with HER2-positive metastatic biliary tract cancer. This treatment was well-tolerated and promising for further trials.
Area of Science:
- Oncology
- Medical Research
- Clinical Trials
Background:
- Metastatic biliary tract cancers (BTC) have limited treatment options and poor prognosis.
- The MyPathway study investigates approved therapies for non-indicated tumors with actionable molecular alterations.
Purpose of the Study:
- To evaluate the efficacy and safety of a dual anti-HER2 regimen (pertuzumab plus trastuzumab) in patients with HER2-positive metastatic BTC.
- To assess the objective response rate (ORR) in this patient population.
Main Methods:
- A non-randomized, multicenter, open-label, phase 2a basket study.
- 39 patients with previously treated metastatic BTC and HER2 amplification/overexpression received intravenous pertuzumab and trastuzumab.
- Objective response rate (ORR) was assessed by investigators using RECIST v1.1.
Main Results:
- An objective response rate (ORR) of 23% (95% CI 11-39) was observed in 39 evaluable patients.
- Grade 3-4 treatment-emergent adverse events occurred in 46% of patients, most commonly elevated liver enzymes.
- No treatment-related serious adverse events or deaths were reported.
Conclusions:
- Pertuzumab plus trastuzumab demonstrated a promising response rate in previously treated HER2-positive metastatic BTC.
- The dual anti-HER2 therapy was well-tolerated, supporting further investigation in randomized controlled trials.
