Pyrotinib Combined With Vinorelbine in HER2-Positive Metastatic Breast Cancer: A Multicenter Retrospective Study

Abstract

IntroductionPyrotinib plus capecitabine has been approved in China for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Meanwhile, vinorelbine is another important chemotherapy option for MBC available in oral and intravenous forms. Thus, pyrotinib plus vinorelbine may represent a new treatment option, particularly for patients with failed capecitabine treatment. This study reported the first real-world data for pyrotinib plus vinorelbine therapy in HER2+ MBC.MethodsHER2+ MBC patients (n = 97) treated with pyrotinib plus vinorelbine in six institutions across China from May 2018 to June 2020 were enrolled. Progression-free survival (PFS), objective response rate (ORR), overall survival (OS), and toxicity profiles were determined.ResultsSixty-seven percent of patients received more than two lines of systematic therapy. Nearly all patients (97.9%) had received trastuzumab and 50.5% were administered lapatinib. When combined with pyrotinib, 74.2% received oral and 25.8% received intravenous vinorelbine. Median PFS (mPFS) was 7.8 (range, 4.7–10.8) months for all patients. The mPFS in patients administered pyrotinib as second-line therapy and third-or-higher-line therapy were 12.0 and 6.4 months, respectively. Patients who received pyrotinib plus oral or intravenous vinorelbine had similar mPFS (7.8 vs. 6.4 months, p = 0.871). The 23 patients with brain metastases had mPFS of 6.3 (range, 3.4–9.2) months. Lapatinib-naïve patients had significantly longer PFS than lapatinib-treated patients (10.8 months vs. 5.6 months, p = 0.020). Median OS was not achieved. The ORR for 96 patients was 34.3%. Common grade 3 and 4 adverse events were diarrhea (22.7%), neutropenia (7.2%), and leukopenia (4.1%).ConclusionsPyrotinib plus vinorelbine therapy demonstrated promising effects in HER2+ MBC with tolerable toxicity, particularly in patients with second-line treatment and without prior lapatinib treatment, as well as in patients with brain metastases. Oral vinorelbine is a useful alternative to the intravenous form when combined with pyrotinib.Clinical Trial Registration[ClinicalTrials.gov], identifier [NCT04517305].

Real-World Analysis of the Efficacy and Safety of a Novel Irreversible HER2 Tyrosine Kinase Inhibitor Pyrotinib in Patients with HER2-Positive Metastatic Breast Cancer

“…The standard chemotherapy agent for combination with pyrotinib or lapatinib is capecitabine, which is mainly based on the fact that capecitabine is the most commonly used chemotherapy drug for mBC patients with resistance to anthracycline and taxanes. 12,[21][22][23] Moreover, both TKIs and capecitabine are oral drugs with much more convenience for patients to take. In real-world clinical practice, for patients who have progressed on previous capecitabine treatment, other chemotherapy agents such as vinorelbine, gemcitabine and taxanes could also be potentially combined with pyrotinib based on their synergistic effect with trastuzumab.…”

Treatment with pyrotinib-based therapy in lapatinib-resistant HER2-positive metastatic breast cancer: a multicenter real-world study

“… 12 Similarly, lapatinib-naïve patients reportedly had a longer PFS than lapatinib-treated patients who received subsequent pyrotinib + vinorelbine therapy. 13 However, another real-world study suggested that pyrotinib provided a significant longer PFS than T-DM1 among patients who initially responded to lapatinib. 14 These results imply that the efficacy of exchanging TKIs might depend on the response to prior TKI treatment.…”

Temporal Heterogeneity of HER2 Expression and Spatial Heterogeneity of 18F-FDG Uptake Predicts Treatment Outcome of Pyrotinib in Patients with HER2-Positive Metastatic Breast Cancer

“…The median PFS was 13.7 months (95% CI, 9.3–18.2) in this study, comparable to that reported in the phase III trial (12.5 months), further proving the efficacy of pyrotinib [ 9 ]. Vinorelbine has been an alternative combinational agent for pyrotinib in patients with previous exposure to capecitabine [ 53 ].…”