Treatment beyond progression and rechallenge with pyrotinib in HER2-positive metastatic breast cancer and brain metastases: A multicenter real-world study.

e13005 Background: Despite advances in treatment, patients with HER2-positive metastatic breast cancer (MBC) continue to face the challenge of drug resistance, highlighting the need to develop new drugs and treatment strategies. Pyrotinib has exhibited substantial efficacy in managing HER2-positive MBC, especially in individuals with brain metastasis (BM). However, real-world data regarding the efficacy of pyrotinib re-treatment remains limited. Methods: In this retrospective, multicenter, real-world study, patients with HER2-positive MBC who progressed during pyrotinib treatment and later continued or resumed pyrotinib-based regimens were enrolled at 17 institutions across China, between August 3, 2018, and November 15, 2023. Patients were divided into two groups according to the re-treatment pattern: the pyrotinib treatment beyond progression (TBP) group and the pyrotinib rechallenge group. The endpoints were progression-free survival (PFS) and overall survival (OS).PFS and OS were estimated using Kaplan–Meier survival curves, with group differences assessed by the log-rank test. Results: A total of 226 participants received pyrotinib TBP, whereas 33 received pyrotinib rechallenge. The median PFS of pyrotinib re-treatment (7.2 vs. 6.3 months, p = 0.51) and the median OS from the initiation of the first pyrotinib treatment (53.0 vs. 43.7 months, p = 0.63) were comparable between the two groups. Among patients with and without BMs before pyrotinib re-treatment, the adjusted median PFS for pyrotinib re-treatment was both 7.2 months (p = 0.18), and the adjusted median OS from the initiation of the first pyrotinib treatment was 43.7 and 53.0 months, respectively. Patients with longer PFS during initial pyrotinib therapy and those who underwent pyrotinib rechallenge after a longer treatment-free interval (TFI) had better OS outcomes (longer vs. shorter initial PFS: 60.9 vs. 37.0 months, p = 0.00014; longer vs. shorter TFI: not reached vs. 32.7 months, p = 0.0026). Conclusions: Pyrotinib TBP and pyrotinib rechallenge both provide potential benefits for patients with HER2-positive MBC, including those with BM. Patients with a longer initial PFS and extended TFI are likely to benefit more from re-treatment, warranting further evaluation. (ISRCTN Identifier: ISRCTN93654271).