Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study
Mené sur 39 patients atteints d'un cancer métastatique des voies biliaires HER2+, cet essai non randomisé de phase IIa évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité d'un traitement combinant pertuzumab et trastuzumab
Background : Systemic therapies for metastatic biliary tract cancers are few, and patients havea median overall survival of less than 1 year. MyPathway evaluates the activity ofUS Food and Drug Administration-approved therapies in non-indicated tumours with potentiallyactionable molecular alterations. In this study, we present an analysis of patients with metastatic biliary tract cancers with HER2 amplification, overexpression, orboth treated with a dual anti-HER2 regimen, pertuzumab plus trastuzumab, from MyPathway. Methods : MyPathway is a non-randomised, multicentre, open-label, phase 2a, multiple basketstudy. Patients aged 18 years and older with previously treated metastatic biliarytract cancers with HER2 amplification, HER2 overexpression, or both and an Eastern Cooperative Oncology Groupperformance status of 0–2 were enrolled from 23 study sites in the USA and receivedintravenous 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-assessedobjective response rate according to Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1. The primary outcome and adverse events were analysed in allpatients who received at least one dose of pertuzumab and trastuzumab. This trialis registered with ClinicalTrials.gov, NCT02091141, and is ongoing. Findings : 39 patients enrolled in the MyPathway HER2 biliary tract cancer cohort between Oct28, 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 39patients 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 inthree (8%) of 39 patients, including increased alanine aminotransferase, aspartateaminotransferase, blood alkaline phosphatase, and blood bilirubin. Serious treatment-emergentadverse events were observed in ten (26%) of 39 patients, of which only abdominalpain occurred in more than one patient (two [5%] of 39). There were no treatment-relatedserious adverse events, treatment-related grade 4 events, or deaths. Interpretation : Treatment was well tolerated in patients with previously treated HER2-positive metastaticbiliary tract cancer. The response rate is promising for the initiation of randomised,controlled trials of pertuzumab plus trastuzumab in this patient population.
The Lancet Oncology 2021