Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): a multicentre, open-label, randomised, controlled, phase 3 trial
Mené en Chine sur des patientes atteintes d'un cancer du sein HER2+ de stade métastatique (âge : 18-70 ans), cet essai de phase III compare l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout du pyrotinib et du lapatinib à la capécitabine, après l'échec du trastuzumab
Background : Despite therapeutic advances in HER2-positive metastatic breast cancer, resistanceto trastuzumab inevitably develops. In the PHOEBE study, we aimed to assess the efficacyand safety of pyrotinib (an irreversible pan-HER inhibitor) plus capecitabine after previous trastuzumab. Methods : This is an open-label, randomised, controlled, phase 3 trial done at 29 hospitals in China. Patients with pathologically confirmed HER2-positive metastatic breast cancer,aged 18–70 years, who had an Eastern Cooperative Oncology Group performance statusof 0 or 1, and had been previously treated with trastuzumab and taxanes were randomlyassigned (1:1) to receive oral pyrotinib 400 mg or lapatinib 1250 mg once daily plusoral capecitabine 1000 mg/m 2 twice daily on days 1–14 of each 21-day cycle. Randomisation was done via a centralisedinteractive web-response system with a block size of four or six and stratified byhormone receptor status and previous lines of chemotherapy for metastatic disease.The primary endpoint was progression-free survival according to masked independentcentral review. Efficacy and safety were assessed in all patients who received atleast one dose of the study drugs. Results presented here are from a prespecifiedinterim analysis. This study is registered with ClinicalTrials.gov, NCT03080805. Findings : Between July 31, 2017, and Oct 30, 2018, 267 patients were enrolled and randomly assigned.134 patients received pyrotinib plus capecitabine and 132 received lapatinib pluscapecitabine. At data cutoff of the interim analysis on March 31, 2019, median progression-free survival was significantly longer with pyrotinib plus capecitabine (12·5 months [95%CI 9·7–not reached]) than with lapatinib plus capecitabine (6·8 months [5·4–8·1];hazard ratio 0·39 [95% CI 0·27–0·56]; one-sided p<0·0001). The most common grade 3or worse adverse events were diarrhoea (41 [31%] in the pyrotinib group vs 11 [8%] in the lapatinib group) and hand–foot syndrome (22 [16%] vs 20 [15%]). Serious adverse events were reported for 14 (10%) patients in the pyrotinibgroup and 11 (8%) patients in the lapatinib group. No treatment-related deaths werereported in the pyrotinib group and one sudden death in the lapatinib group was considered treatment related. Interpretation : Pyrotinib plus capecitabine significantly improved progression-free survival comparedwith that for lapatinib plus capecitabine, with manageable toxicity, and can be consideredan alternative treatment option for patients with HER2-positive metastatic breastcancer after trastuzumab and chemotherapy.
The Lancet Oncology 2021