Pyrotinib plus capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases (PERMEATE): a multicentre, single-arm, two-cohort, phase 2 trial
Mené en Chine sur 78 patientes atteintes d'un cancer du sein HER2+ et présentant des métastatases cérébrales (durée médiane de suivi : 15,7 mois), cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective intracrânienne, et la toxicité d'un traitement combinant pyrotinib et capécitabine
Background : Patients with HER2-positive metastatic breast cancer have a high risk of developing brain metastases. Efficacious treatment options are scarce. We investigated the activity and safety of pyrotinib plus capecitabine in patients with HER2-positive metastatic breast cancer and brain metastases.
Methods : We did a multicentre, single-arm, two-cohort, phase 2 trial in eight tertiary hospitalsin China. Patients aged 18 years or older who had radiotherapy-naive HER2-positivebrain metastases (cohort A) or progressive disease after radiotherapy (cohort B),with an Eastern Cooperative Oncology Group performance status of 0–2, received pyrotinib400 mg orally once daily, and capecitabine 1000 mg/m2 orally twice daily for 14 days, followed by 7 days off every 3 weeks until diseaseprogression or unacceptable toxicity. The primary endpoint was confirmed intracranial objective response rate by investigator assessment according to the Response EvaluationCriteria In Solid Tumours (version 1.1). Activity and safety were analysed in patientswith at least one dose of study drug. The study is ongoing, but recruitment is complete.The study is registered with ClinicalTrials.gov, NCT03691051.
Findings : Between Jan 29, 2019, and July 10, 2020, we enrolled 78 women: 51 (86%) of 59 patientsin cohort A and 18 (95%) of 19 patients in cohort B had previous exposure to trastuzumab.Median follow-up duration was 15·7 months (IQR 9·7–19·0). The intracranial objectiveresponse rate was 74·6% (95% CI 61·6–85·0; 44 of 59 patients) in cohort A and 42·1%(20·3–66·5; eight of 19 patients) in cohort B. The most common grade 3 or worse treatment-emergentadverse event was diarrhoea (14 [24%] in cohort A and four [21%] in cohort B). Two(3%) patients in cohort A and three (16%) in cohort B had treatment-related serious adverse events. No treatment-related deaths occurred.
Interpretation : To our knowledge, this is the first prospective study showing the activity and safetyof pyrotinib plus capecitabine in patients with HER2-positive breast cancer and brain metastases, especially in radiotherapy-naive population. This combination deservesfurther validation in a randomised, controlled trial.
The Lancet Oncology , résumé, 2021