A Real-world Study Of Pyrotinib In The Treatment Of HER2-positive Advanced Breast Cancer

Purpose:To explore the efficacy and safety of pyrotinib in a real-world setting for HER2-positive advanced breast cancer,and subgroup analyses were conducted based on different clinicopathological features to further explore the effects of treatment lines on the efficacy of pyrotinib in real-world studies,including general patient characteristics,tumor nature,and various lines of treatment prior to initiation of pyrotinib.Method:A list of HER2-positive advanced breast cancer patients treated with pyrotinib alone or in combination with other drugs at the Cancer Center of the First Hospital of Jilin University from September 2018 to December 2022 was collected.Patients eligible for this study were screened out according to inclusion and exclusion criteria,and the basic information of individual patients and information related to previous treatment were further collected,including diagnosis time,pathological type,molecular typing,tumor stage,whether surgery,radiotherapy,and postoperative maintenance treatment.Information on each progression or recurrence(time,site,pathology,treatment regimen and course,efficacy evaluation),as well as the duration,efficacy evaluation,and adverse events(including time,type,severity,duration,measures,and outcome)of the patient’s treatment with pyrotinib.Adverse events were evaluated according to the NCI-CTC AE<5.0> classification criteria for drug AE.Progression-free survival(PFS),objective response rate(ORR),clinical benefit rate(CBR)and the occurrence of adverse events were statistically analyzed by SPSS 26.0software.Results:1.A total of 134 eligible patients were enrolled in this study by the end of follow-up,December 2022.The median age of the population was 54.0 years(interquartile interval was 46.0 to 59.3 years).94 cases(70.1%)were postmenopausal.The ECOG score was 0 in 88 cases(65.7%).24 cases(17.9%)were newly diagnosed at stage IV.103 cases(76.9%)underwent surgical treatment;124 cases(92.5%)were diagnosed with invasive ductal carcinoma.80 cases(59.7%)were grade 2 histology.62 cases(46.3%)were hormone-receptor expression.71 cases(53.0%)were vascular infiltration.96 cases(71.6%)with lymph node metastasis.82 cases(61.2%)with visceral metastasis.32 cases(23.9%)with brain metastases.117 cases(87.3%)had received taxine/anthracycline treatment before;109 cases(81.3%)had received anti-HER2 therapy before;17 cases(12.7%)had previously received small molecule TKI drugs;11 cases(8.2%)had received ADC drugs before;82 cases(61.2%)had received radiotherapy before;Among the included population,37 cases(27.6%),46cases(34.3%)and 51 cases(38.1%)had 1,2 and 3 or more lines of late treatment,respectively.2.The median progression-free survival(m PFS)of the population was about11.1 months.Significant univariate cox regression factors included ECOG score,lymph node metastasis,visceral metastasis,ADC drug therapy,small molecule TKI drug therapy,and treatment line number.Multivariate cox regression analysis showed that visceral metastasis and ADC drug therapy were independent influencing factors of PFS.3.Short-term efficacy analysis was available for all 134 patients included,with an objective response rate(ORR)of 64.2% and a clinical benefit rate(CBR)of 90.3%.Univariate Logistic regression analysis revealed age,lymph node metastasis,prior treatment with taxyl-anthracycline,and the amount of treatment lines to be statistically significant.Multivariate Logistic regression analysis,however,demonstrated that age and the number of treatment lines were independent determinants of ORR.4.Diarrhea was still the most important adverse event in the course of pyrotinib administration,accounting for more than 90% of the total population in the study,followed by hand-foot syndrome.Symptomatic treatment could be given to alleviate the symptoms of related adverse events,which basically did not affect subsequent administration,and grade 3 and above adverse events were less frequent.Conclusion:1.Pyrotinib has shown good antitumor activity in a real-world study of advanced HER2-positive breast cancer,with a median progression-free survival(m PFS)of 11.1months,an objective response rate(ORR)of 64.2%,and a clinical benefit rate(CBR)of 90.3%.2.Patients with ECOG score of 0,no lymph node metastasis,no visceral metastasis,no ADC drug therapy,no TKI drug therapy and late first-line therapy had significantly prolonged PFS.An analysis of multivariate cox revealed that pyrotinib treatment for HER2-positive advanced breast cancer was not dependent on visceral metastases or prior ADC therapy.3.Objective response rates were higher in patients aged 25-40 years without lymph node metastasis,who had not received prior taxine/anthracycline therapy and first-line therapy.Age and treatment lines were independent factors of objective response rate(ORR).4.Pyrotinib shows good antitumor activity in patients with brain metastases.5.Pyrotinib remains effective in patients who have received prior treatment with taxus/anthracyclines and/or anti-HER2.6.Diarrhea was the most common adverse event associated with pyrotinib treatment,and overall adverse events were controllable with few high-grade adverse events.