Lapatinib concentration in cerebrospinal fluid in two patients with HER2-positive metastatic breast cancer and brain metastases

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].

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Faculty of 1000 evaluation for Phase I trial combining temozolomide plus lapatinib for the treatment of brain metastases in patients with HER2-positive metastatic breast cancer: the LAPTEM trial.

F1000 - Post-publication peer review of the biomedical literature ◽

10.3410/f.718102079.793485106 ◽

2013 ◽

Author(s):

Ana Maria Gonzalez-Angulo

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Brain Metastases ◽

Phase I ◽

Phase I Trial ◽

Metastatic Breast ◽

Her2 Positive

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WJOG6110B (ELTOP): Randomized phase II trial comparing trastuzumab plus capecitabine (HX) and lapatinib plus capecitabine (LX) in HER2-positive metastatic breast cancer patients previously treated with trastuzumab and taxanes.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.tps659 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. TPS659-TPS659 ◽

Cited By ~ 1

Author(s):

Toshimi Takano ◽

Hideharu Kimura ◽

Kazuto Nishio ◽

Takeharu Yamanaka ◽

Yoshinori Ito ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Brain Metastases ◽

Randomized Trial ◽

Phase Ii ◽

Phase Ii Trial ◽

Metastatic Breast ◽

Her2 Positive ◽

Randomized Phase Ii ◽

Previously Treated

TPS659 Background: In patients with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab and taxanes, there are now two standard strategies: trastuzumab beyond progression or switch to lapatinib. A randomized trial comparing trastuzumab plus capecitabine (HX) and capecitabine alone (X) after first-line trastuzumab-based chemotherapy (GBG-26) showed that HX was superior to X in terms of time to progression (TTP). Another randomized trial comparing lapatinib plus capecitabine (LX) and X in patients previously treated with anthracyclines, taxanes, and trastuzumab (EGF100151) showed that LX was superior to X in terms of TTP. To evaluate which strategy is better, we are conducting an open-label, randomized phase II trial comparing HX and LX. Methods: Primary endpoint is progression-free survival, and secondary endpoints are overall response rate, overall survival, proportion of patients progressing brain metastases as site of first progression, and safety. Major eligibility criteria include: (1) HER2-positive MBC, (2) previously treated with taxanes, (3) disease progression or distant relapse while receiving trastuzumab, (4) previously untreated with capecitabine, S-1, and anti-HER2 drugs other than trastuzumab, (5) previously treated with no more than two chemotherapy regimens for MBC, (6) no symptomatic brain metastases (asymptomatic brain metastases are allowed), and (7) baseline left ventricular ejection fraction ≥50%. Patients in the HX arm receive capecitabine 2,500 mg/m2/day on days 1 to 14 plus trastuzumab (8 mg/kg loading dose and 6mg/kg thereafter) on day 1 every 3 weeks. Patients in the LX arm receive capecitabine 2,000 mg/m2/day on days 1 to 14 plus lapatinib 1250 mg/day on days 1 to 21 every 3weeks. Large-scale biomarker analyses are also performed to explore predictive factors of trastuzumab or lapatinib efficacy. We are investigating biomarkers related to HER family and other receptors, PI3K/Akt pathways, ligands, FcγR, circulating tumor cells, and so on. This study has just begun and 7 of planned 170 patients have been enrolled.

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