Pyrotinib Combined with Vinorelbine in Patients with Previously Treated HER2-Positive Metastatic Breast Cancer: A Multicenter, Single-arm, Prospective Study
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Purpose This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.
Abstract
Purpose This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.
참고문헌 (34)
- Sung H, "Global cancer statistics 2020 : GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries", CA Cancer J Clin, 71, pp.209~249 (2021)
- Waks AG, "Breast cancer treatment : a review", JAMA, 321, pp.288~300 (2019)
- Owens MA, "HER2 amplification ratios by fluorescence in situ hybridization and correlation with immunohistochemistry in a cohort of 6556 breast cancer tissues", Clin Breast Cancer, 5, pp.63~69 (2004)
- Slamon DJ, "Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2", N Engl J Med, 344, pp.783~792 (2001)
- Swain SM, "Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer", N Engl J Med, 372, pp.724~734 (2015)
- Verma S, "Trastuzumab emtansine for HER2-positive advanced breast cancer", N Engl J Med, 367, pp.1783~1791 (2012)
- Cortes J, "Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer", N Engl J Med, 386, pp.1143~1154 (2022)
- Geyer CE, "Lapatinib plus capecitabine for HER2-positive advanced breast cancer", N Engl J Med, 355, pp.2733~2743 (2006)
- Awada A, "Neratinib plus paclitaxel vs trastuzumab plus paclitaxel in previously untreated metastatic ERBB2-positive breast cancer : the NEfERT-T randomized clinical trial", JAMA Oncol, 2, pp.1557~1564 (2016)
- Li X, "Discovery and development of pyrotinib : a novel irreversible EGFR", HER2 dual tyrosine kinase inhibitor with favorable safety profiles for the treatment of breast cancer, 2017, pp.110, 51~61
- Gourd E, "Pyrotinib shows activity in metastatic breast cancer", Lancet Oncol, 18, pp.e643~ (2017)
- Li Q, "Safety, efficacy, and biomarker analysis of pyrotinib in combination with capecitabine in HER2-positive metastatic breast cancer pati-ents : a phase I clinical trial", Clin Cancer Res, 25, pp.5212~5220 (2019)
- Ma F, "Pyrotinib or lapatinib combined with capecitabine in HER2-positive metastatic breast cancer with prior taxanes, anthracyclines, and", or trastuzumab : a randomized, phase II study, 2019, pp.37, 2610~2619
- Xu B, "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", Lancet Oncol, 22, pp.351~360 (2021)
- Pegram MD, "Rational combinations of trastuzumab with chemotherapeutic drugs used in the treatment of breast cancer", J Natl Cancer Inst, 96, pp.739~749 (2004)
- Burstein HJ, "Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer : the trastuzumab and vinorelbine or taxane study", Cancer, 110, pp.965~972 (2007)
- Andersson M, "Phase III randomized study comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab as first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer : the HERNATA study", J Clin Oncol, 29, pp.264~271 (2011)
- Li Y, "Pyrotinib combined with vinorelbine in HER2-positive metastatic breast cancer : a multicenter retrospective study", Front Oncol, 11, pp.664429~ (2021)
- Xie Y, "Pyrotinib plus vinorelbine versus lapatinib plus capecitabine in patients with previously treated HER2-positive metastatic breast cancer : a multicenter, retrospective study", Front Oncol, 11, pp.699333~ (2021)
- Yin S, "Efficacy and safety of pyrotinib-containing regimen in the patients with HER2-positive metastatic breast cancer : a multicenter real-world study", Cancer Med, 12, pp.2333~2344 (2023)
- Wolff AC, "Human epidermal growth factor receptor 2 testing in breast cancer : American Society of Clinical Oncology", College of American Pathologists clinical practice guideline focused update, 2018, pp.36, 2105~2122
- Yan M, "Pyrotinib plus capecitabine for human epidermal growth factor receptor 2-positive metastatic breast cancer after trastuzumab and taxanes(PHENIX) : a randomized, double-blind, placebo-controlled phase 3 study", Transl Breast Cancer Res, 1, pp.1~13 (2020)
- Singla H, "Role of genomic alterations in HER2 positive breast carcinoma : focus on susceptibility and trastuzumab-therapy", Curr Cancer Drug Targets, 17, pp.344~356 (2017)
- Vu T, "Trastuzumab : updated mechanisms of action and resistance in breast cancer", Front Oncol, 2, pp.62~ (2012)
- Singla H, "HER2 tyrosine kinase inhibitors in the sensitization to cancers resistant to HER2 antibodies", Crit Rev Oncog, 25, pp.241~250 (2020)
- Su B, "Apatinib exhibits synergistic effect with pyrotinib and reverses acquired pyrotinib resistance in HER2-positive gastric cancer via stem cell factor", c-kit signaling and its downstream pathways, 2021, pp.24, 352~367
- Marty M, "Oral vinorelbine pharmacokinetics and absolute bioavailability study in patients with solid tumors", Ann Oncol, 12, pp.1643~1649 (2001)
- Bonneterre J, "Phase I and pharmacokinetic study of weekly oral therapy with vinorelbine in patients with advanced breast cancer(ABC)", Ann Oncol, 12, pp.1683~1691 (2001)
- Petain A, "Effect of ethnicity on vinorelbine pharmacokinetics : a population pharmacokinetics analysis", Cancer Chemother Pharmacol, 84, pp.373~382 (2019)
- Jassem J, "A multicenter randomized phase II study of oral vs. intravenous vinorelbine in advanced non-small-cell lung cancer patients", Ann Oncol, 12, pp.1375~1381 (2001)
- Yang Y, "A randomised, multicentre open-label phase II study to evaluate the efficacy, tolerability and pharmacokinetics of oral vinorelbine plus cisplatin versus intravenous vinorelbine plus cisplatin in Chinese patients with chemotherapy-naive unresectable or metastatic non-small cell lung cancer", J Thorac Dis, 11, pp.3347~3359 (2019)
- Huang L, "Oral vinorelbine versus intravenous vinorelbine, in combination with epirubicin as first-line chemotherapy in Chinese patients with metastatic breast cancer", Cancer Chemother Pharmacol, 85, pp.205~215 (2020)
- Schott S, "Acceptance of oral chemotherapy in breast cancer patients : a survey study", BMC Cancer, 11, pp.129~ (2011)
- Strada MR, "Intravenous or oral vinorelbine plus capecitabine as first-line treatment in HER2-metastatic breast cancer : joint analysis of 2 consecutive prospective phase II trials", Clin Breast Cancer, 12, pp.30~39 (2012)