Observational Study Of Pyrotinib In The Treatment Of Her-2 Positive Advanced Breast Cancer

BackgroundHuman epidermal growth factor receptor-2(Her-2)is overexpressed or amplified in 20%-30%of breast cancer patients,which is more invasive,recurs in a shorter period of time,has a worse prognosis,and has poor tumor-free survival and overall survival compared with other types of breast cancer.The emergence of a variety of anti-HER-2 targeted drugs has significantly improved the treatment status and prognosis of HER-2 positive breast cancer,but there are still a large number of patients with HER-2 positive breast cancer who have not met their treatment needs.Pyrotinib is a new irreversible pan-ErbB receptor tyrosine kinase inhibitor.Pyrotinib can covalently bind to the ATP binding site of the intracellular kinase region of EGFR/HER-1,HER-2,HER-4,preventing the formation of HER family homo/heterodimers,inhibiting autophosphorylation and blocking the transmission of downstream signals,which could have inhibited tumor growth.Phase Ⅰ,Ⅱ,and Ⅲclinical trials of pyrotinib all confirmed its promising antitumor activity and controllable adverse reactions.PurposeThis study aims to observe the efficacy and the factors of pyrotinib in the treatment of HER-2 positive patients in advanced breast cancer,adverse reactions,and clinical characteristics of the well effected population;Analyze the related factors affecting the efficacy of pyrotinib treatment.according to which could provide real-world efficacy and safety data for pyrotinib in the treatment of HER2-positive advanced breast cancer,and increased clinical experience in the treatment of pyrotinib in among the HER-2 positive advanced breast cancer.MethodsWe prospectively collected and retrospectively analyzed HER2-positive breast cancer patients who treated by pyrotinib among several hospitals in Shandong Province from August 2018 to July 2019.Inclusion criteria:(1)Breast cancer confirmed by histopathology and HER-2 positive by immunohistochemistry or FISH,regardless of whether the hormone receptors ER and PR are positive;(2)Pyrotinib targeted therapy,regardless of the combination of drugs;(3)Whatever anti-HER-2 targeted therapy in the past;(4)In the past,no matter what chemotherapy with taxanes or anthracyclines were used.By collecting the basic information and clinical pathology data of the selected patients,using a questionnaire for telephone follow-up,recording the patient’s treatment effect and adverse drug reactions during treatmentof pyrotinib,etc.In this study,a total of 64 breast cancer patients who met the inclusion criteria were obtained.IBM SPSS 26.0 software was used to analyze the population baseline characteristics,pathological characteristics,previous treatment history,adverse reactions and the efficacy of pyrotinib.Then further explore the related factors that affect the efficacy of pyrotinib treatment.ResultsAs of the follow-up end date,a total of 64 patients with HER2-positive breast cancer were treated with pyrotinib were observed.Among these 64 patients,2 patients had discontinued treatment due to surgery,20 patients have discontinued treatment,other 44 patients with breast cancer are still receiving pyrotinib.The main reasons for patients to stop the treatment including:disease progression,intolerable side effects,death,and economic reasons.The median age was 54 years.34(53.1%)patients were hormone receptor positive,53(82.8%)patients were distant metastases,of which 37(57.8%)patients were visceral metastases,11(17.2%)patients had brain metastases.and 60(93.8%)of all patients had previously received taxanes or anthracyclines chemicals treatment,59(92.2%)patients had been treated with trastuzumab and/or Ado-trastuzumab emtansine(TDM-1)in the(neo-)adjuvant phase,the metastatic phase,or both.Of which 26(40.6%)patients were treated in the(neo-)adjuvant phase.23(35.9%)patients in the metastatic phase,10(15.6%)patients in both phases;11(17.2%)patients were treated with lapatinib after trastuzumab and/or TDM-1 treatment failed.Of the total population,47 patients achieved objective response,with an objective response rate(ORR)of 73.4%,and 56 patients benefited clinically,with a clinical benefit rate of 87.5%.It has been observed that patients who have been treated with trastuzumab and patients with brain metastases still have good results.Statistical analysis showed that after trastuzumab and/or TDM-1 treatment failed,lapatinib anti-Her-2 treatment and the number of visceral metastatic organs may be related to objective remission.Patients with receiving lapatinib after trastuzumab and/or TDM-1 treatment failed(HR=2.264,95%CI 0.875-5.858,log-rank p=0.043)and visceral metastasis(HR=3.645,95%CI 1.052-12.621,log-rank p=0.028)have higher risk of progression or death.And the analysis showed that visceral metastasis was a risk factor for progression-free survival events(p<0.05).Diarrhea(28.1%),hand-foot syndrome(17.2%),and leukopenia(9.4%)were the most common toxic effects associated with pyrotinib treatment.Conclusion1.Pyrotinib is effective in the treatment of patients with HER-2 positive advanced breast cancer,and the objective response rate(ORR)and clinical benefit rate(CBR)were higher.2.The following clinical and pathological conditions of HER2-positive advanced breast cancer patients with the treatment of pyrotinib are effective:regardless of menopause,surgery status,histological types,pathological grades,tumor size,vascular tumor thrombus,lymph nodes status,hormone receptor status,distant metastasis status,whether visceral metastasis,the number of visceral metastasis organs,previous trastuzumab,anthracycline/taxanes chemotherapy,brain metastasis,contralateral breast.Whether the cancer has metastasized,and what chemotherapy drugs are used in combination with pyrotinib.3.Lapatinib treatment after previous trastuzumab and/or TDM-1 treatment failure is an independent risk factor for objective response.The first-line trastuzumab and/or TDM-1 and the second-line lapatinib can benefit from the posterior pyrotinib treatment,but the second-line patients who have not received lapatinib have a higher objective response rate and longer progression-free survival.4.Those without visceral metastasis had higher objective response rate and longer progression-free survival than those with visceral metastasis,and had a lower risk of progression/death.5.Pyrotinib combined with capecitabine,taxanes,and vinorelbine all have good reactions.6.The most common adverse reactions of pyrotinib are diarrhea,hand-foot syndrome,which could be controllable.