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Zhi Yang, Wei-Da Fu, Hua-Yan Gu, Jia-Ling Ding, Gui-Long Guo Department of Breast Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of ChinaCorrespondence: Gui-Long Guo, Email guoguilong@sina.comPurpose: To explore the efficacy and safety of pyrotinib in a real-world setting in a population with HER2-positive advanced breast cancer, subgroup analysis was conducted based on different clinicopathological features to further explore the general characteristics of patients, tumor nature, and the effect of various lines of treatment before patients started pyrotinib on the efficacy of pyrotinib in the real-world study.Methods: The clinical pathological characteristics, drug efficacy and related adverse reactions of HER2-positive MBC patients treated with pyrotinib in six hospitals in Southeast Zhejiang Province from February 2018 to December 2023 were collected and analyzed retrospectively.Results: A total of 342 patients with HER2-positive MBC were enrolled. The median follow-up time of 42.0 months. The median age of the overall population was 52 years (range from 25– 90 year old). Median progression-free survival in the total population was 10.0 months, the median overall survival was 29.0 months. The (objective response rate, ORR) was 40.35% and the (disease control rate, DCR) was 83.92%. The median progression-free survival (PFS) in the total population was 10.0 months, the median overall survival was 29.0 months. And pyrotinib had better mPFS for advanced first-line treatment than for second-third-line and beyond(14.0 months vs.10.0 months vs.6.0 months, P< 0.001). Multivariate Cox regression analysis showed that ECOG, HER2 status, brain metastasis, liver metastasis, number of pyrotinib treatment lines, previous lapatinib treatment, combined capecitabine therapy and trastuzumab resistance were independent prognostic factors for PFS. Diarrhea was the most common adverse reaction (ADR) in 205 patients (59.94%), which could be controlled by antidiarrheal drugs.Conclusion: This multicenter study suggested that the use of pyrotinib for HER2 positive MBC had a relatively good efficacy, especially for those who received first-line pyrotinib treatment and those who were sensitive to previous trastuzumab treatment. Patients with brain metastasis and liver metastases also benefit from pyrotinib treatment, especially for patients treated with brain radiotherapy and/or surgery. ECOG, HER2 status, brain metastasis, liver metastasis, number of pyrotinib treatment lines, previous lapatinib treatment, combined capecitabine therapy and trastuzumab resistance were independent prognostic factors for PFS in HER2 Positive MBC patients treated with pyrotinib. The most common adverse reaction associated with pyrotinib is diarrhea, which can be well controlled through antidiarrheal treatment. Pyrotinib combined with vinorelbine has similar efficacy to pyrotinib combined with capecitabine and has fewer side effects, and can be used as an alternative to capecitabine.Keywords: pyrotinib, HER2 positive metastatic breast cancer, real-world study, efficacy, safety

Qingqing Gu, Mingzhi Zhu, Yanyan Wang, Yuanting Gu The Second Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Yuanting Gu; Yanyan Wang, The Second Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China, Tel +86-371-66913114, Fax +86-371-66964992, Email guyuanting2009@163.com; fccwangyy22@zzu.edu.cnPurpose: To evaluate the efficacy and safety of a pyrotinib-based therapy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) in the real world.Methods: Clinical data of 218 patients with HER2-positive MBC who received a pyrotinib-based therapy from January 2020 to March 2023 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed.Results: Finally, 195 patients were included in the efficacy cohort. The median progression-free survival (PFS) in the total population is 12.4 months (95% CI, 9.8– 15.0 months). More than half of the patients in the efficacy cohort received pyrotinib mono-targeted therapy (103 cases, 52.8%). Among the remaining patients, 74 (37.9%) patients chose a combined trastuzumab-targeted therapy and 17 (8.7%) chose to combine inetetamab. Median PFS in the pyrotinib group vs pyrotinib plus trastuzumab group was 10.5 months vs 20.1 months (P< 0.001). The median PFS of primary trastuzumab resistance population reached to 20.1 months in pyrotinib plus trastuzumab group. Double-targets’ advantage was also observed in the brain metastases subgroup (17.9 months vs 10.0 months, P=0.386). The patients who received pyrotinib plus inetetamab as second and higher-line treatment reached a median PFS of 7.9 months (95% CI, 4.0– 11.8 months). Forty-one (19.8%) of 207 patients included in the safety cohort experienced grade 3 or higher diarrhea, the most common adverse event in safety analysis, and no adverse event-related deaths.Conclusion: The combination of pyrotinib and trastuzumab demonstrated promising efficacy in the treatment of HER2-positive metastatic breast cancer, including those who had primary resistance to trastuzumab and brain metastases. Pyrotinib plus trastuzumab is expected to be a potent option in the first-line. Additionally, the concurrent administration of pyrotinib and inetetamab could be an alternative to consider in the second and higher-line treatment for metastatic breast cancer. The adverse reactions of pyrotinib were tolerable in general.Keywords: pyrotinib, HER2, metastatic breast cancer, trastuzumab, inetetamab

Congcong Wang,1,&ast; Jinyu Xiang,1,&ast; Qingyu Zhang,1 Jing Li,1 Yanqing Liu,2 Jiannan Liu1 1Department of Oncology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shangdong, 264000, People’s Republic of China; 2Department Brest Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shangdong, 264000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiannan Liu, Department of Oncology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20 Yuhuangding East Road, Yantai, 264000, People’s Republic of China, Email ljnwcc@163.com Yanqing Liu, Department Brest Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20 Yuhuangding East Road, Yantai, 264000, People’s Republic of China, Email liuyanqing927@163.comAim: Approximately 50% of patients diagnosed with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (BC) are estimated to develop brain metastases (BMs). This study was aimed to assess the intracranial efficacy and survival benefits of pyrotinib and capecitabine combination therapy in the treatment of BMs in patients with HER2-positive BC.Methods: A total of 56 HER2-positive BC patients with BMs were treated with 400 mg pyrotinib once daily along with 1000 mg/m2 capecitabine twice daily for 14 days in 21-day cycles. The patients were allocated into three cohorts: (1) Cohort A composed of patients with newly diagnosed BMs without prior local radiotherapy, (2) Cohort B included patients with stable post-local radiotherapy, and (3) Cohort C composed of patients with progression following local radiotherapy. The primary endpoint was the intracranial objective response rate (CNS-ORR), while secondary endpoints included intracranial disease control rate (CNS-DCR), progression-free survival (PFS), overall survival (OS), safety, as well as QoL.Results: The observed CNS-ORR CNS-ORR of 72.73% (95% CI 51.85– 86.85%) in cohort A, 55% (95% CI 34.21– 74.18%) in cohort B, and 42.86% (95% CI 21.38– 67.41%) in cohort C. The mPFS was 11 months, 8.4 months, and 5.2 months in cohorts A, B, and C, respectively. Diarrhea, accounting for 23.21% of all the patients, was the most common grade 3/4 adverse event related with treatments (6/22 [27.3%] in cohort A, 4/20 [20.0%] in cohort B, and 3/14 [21.4%] in cohort C). However, there were no deaths related with treatments observed. Importantly, the QoL was efficiently maintained throughout the treatment duration.Conclusion: Pyrotinib and capecitabine combination therapy proved significant effectiveness as well as tolerability in treating HER2-positive BC with BMs, yielding satisfactory results, especially in radiotherapy-naive population.Keywords: breast cancer, brain metastases, pyrotinib, capecitabine, HER2, radiotherapy

Jie Huang,1,&ast; Wenqiang Zhu,1,&ast; Qiangzhi Duan,2,&ast; Chaomang Zhu,1 Xueling Shi,1 Hongyu Zhao,1 Peng Cai,1 Duojie Li1 1Department of Radiotherapy, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, People’s Republic of China; 2Department of Radiotherapy, The 2nd Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Duojie Li, Department of Radiotherapy, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, People’s Republic of China, Tel/Fax +86-139-5633-2626, Email liduojie@163.comPurpose: To explore the efficacy and safety of pyrotinib combined with different radiotherapy modes in human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) patients with brain metastasis (BM).Patients and Methods: This study is a retrospective analysis of patients diagnosed with BM who underwent treatment with pyrotinib between November 2018 and April 2023. A total of 66 patients were administered radiotherapy in conjunction with pyrotinib (Group A), while 26 patients received pyrotinib as a standalone treatment (Group B). Within Group A, 18 patients underwent conventional fractionated radiotherapy (2Gy/F), while 48 patients received hyperfractionated radiotherapy (HFRT) (≥ 3Gy/F). The primary endpoints were intracranial progression-free survival (IC-PFS) and overall survival (OS). The secondary endpoints were objective response rate (ORR) and clinical benefit rate (CBR).Results: The ORR of Group A was 54.5% (36/66), while the ORR of Group B was 34.6% (9/26) (P= 0.047). The CBR of Group A was 89.4% (59/66) and that of Group B was 69.2% (18/26) (P= 0.041). The IC-PFS between Group A and Group B were 12 months and 8 months, respectively (P< 0.001), and the OS were 20 months and 16 months, respectively (P= 0.065). In Group A, the IC-PFS and OS between the conventional fractionation radiotherapy group and the HFRT group were 10 months and 12 months, respectively (P= 0.001) and 16 months and 24 months, respectively (P< 0.001). No serious adverse reactions were observed in Group A and Group B.Conclusion: For HER2-positive BC patients with BM, it is recommended to adopt the treatment mode of HFRT combined with pyrotinib, which can improve the local control and survival of patients.Keywords: breast cancer, human epidermal growth factor receptor type 2, brain metastasis, pyrotinib, radiation therapy, hyperfractionated radiotherapy

Jing Liu,1,&ast; Xianglu Sun,2,&ast; Qianyu Du,3 Jinghao Yao,1,4 Mengfen Dai,1 Qianqian Cheng,1 Han Xu,5 Yawei Li,6 Xiuli Liu,7 Mingliang Zhang,8 Yongchun Zhou,2 Yan Yang1 1Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, People’s Republic of China; 2Department of Radiation Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, People’s Republic of China; 3Department of Medical Oncology, Suzhou Municipal Hospital, Suzhou, Anhui, 234000, People’s Republic of China; 4Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230000, People’s Republic of China; 5Department of Medical Oncology, The Third People’s Hospital of Bengbu, Bengbu, Anhui, 233000, People’s Republic of China; 6Department of Medical Oncology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233040, People’s Republic of China; 7Department of Oncology, The Fifth People’s Hospital of Fuyang, Fuyang, Anhui, 236000, People’s Republic of China; 8Department of Oncology Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Yang, Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, People’s Republic of China, Tel/Fax +86 552 3086178, Email qiannianhupo@163.com Yongchun Zhou, Department of Radiation Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, People’s Republic of China, Tel/Fax +86 552 3086845, Email zhouyongchun_1@hotmail.comPurpose: To explore the efficacy, safety, and potential factors influencing efficacy and outcome of pyrotinib-based therapy in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) in complex clinical practice.Methods: Real-world data for HER2-positive MBC patients treated with pyrotinib-based regimens from 6 hospitals in Northern Anhui, China, from September 2018 to February 2022, were retrospectively collected, and clinicopathological features, efficacy, prognosis, and safety were analyzed. Potential influencing factors including baseline serum vascular endothelial growth factor-A (VEGF-A) for evaluating pyrotinib’s treatment response and outcome were also explored.Results: A total of 169 patients with HER2-positive MBC were enrolled. The objective response rate (ORR), disease control rate (DCR), and median progression-free survival (mPFS) of the overall cohort were 65.1%, 87.6%, and 12.4 months, respectively. Pyrotinib is highly beneficial as different treatment lines and appears to be a feasible strategy both in combination with chemotherapeutic drugs and alone. The mPFS values were 16.5 months, 12.4 months, and 9.3 months in the first, second, and third-or-higher lines of anti-HER2 therapy, respectively (P=0.027). The most common adverse event (AE) was diarrhea (88.2%), and patients with < grade 3 diarrhea achieved a longer mPFS than patients with ≥ grade 3 diarrhea (13.3 months vs 6.9 months, P=0.007). Among the patients with available baseline VEGF-A data, the ORR was 43.5% in patients with a high level of VEGF-A, compared to 81.5% in patients with a low level of VEGF-A (P=0.005). Moreover, patients in the VEGF-A-high group exhibited a shorter mPFS time than those in the VEGF-A-low group (7.8 months vs 19.1 months, P=0.004). Further analysis demonstrated AE of diarrhea and VEGF-A at baseline to be independent prognostic factors for PFS.Conclusion: Pyrotinib-based regimens showed promising efficacy, with manageable tolerance, and AE occurrence of severe diarrhea and baseline level of serum VEGF-A are helpful in predicting the treatment outcome of pyrotinib in HER2-positive MBC.Keywords: breast cancer, HER2, pyrotinib, efficacy, prognostic factor, vascular endothelial growth factor A

Yan Li, Xiaoping Ma, Zhenhui Zhao, Li Li, Chunyan Gao, Dan Liu, Bingyu Li, Bing Zhao Department of Breast Cancer, Affiliated Tumor Hospital of Xinjiang Medical University, The Clinical Research Center of Breast Tumor and Thyroid Tumor in Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, 830011, People’s Republic of ChinaCorrespondence: Bing Zhao, Affiliated Tumor Hospital of Xinjiang Medical University, No. 789 Suzhou East Street, Urumqi, Xinjiang, 830011, People’s Republic of China, Tel +86 991 781 9142, Email doctorcrystal@163.comIntroduction: According to the latest global cancer data released by WHO in 2020, the incidence of breast cancer (BC) has been the most prevalent, and the mortality rate of female malignant tumor ranks the first.Methods: To evaluate toxicity and efficacy regarding oral Pyrotinib for elderly patients with advanced HER2-positive breast cancer (BC) in Xinjiang, 45 elderly patients having advanced HER2-positive BC with age ≥ 65 years and receiving Pyrotinib-based combined therapy from January 2019 to May 2021 in Xinjiang were enrolled in this study. PFS, CBR, ORR and drug-related adverse events (AE) of oral Pyrotinib in the patients were retrospectively analyzed. All 45 patients completed the efficacy evaluation.Results: Total ORR and CBR of the whole group was 37.8% and 77.8%, respectively. There were 14 patients with brain metastases (31.1%), with a median PFS of 6.8 months (95% CI: 5.4~9.8). In terms of the number of treatment lines, mPFS for line 1– 2 was 8.3 months (95% CI: 6.3~11.4), and mPFS for line ≥ 3 was 3.3 months (95% CI: 2.7~5.1). At the final maintenance dose, mPFS at standard doses of 400mg, 320mg and 240mg were 9.1 months (95% CI: 4.1~9.5), 8.3 months (95% CI: 4.3~12.2) and 4.8 months (95% CI: 2.1~7.5), respectively.Discussion: Applying Pyrotinib in elderly patients, the main adverse reaction was diarrhea, accounting for 88.9% (40/45). Pyrotinib is safe and effective for elderly patients with advanced HER2 positive BC.Keywords: HER2, breast cancer, Pyrotinib, toxicity, adverse events, elderly

Suyao Li,1,&ast; Qing Liu,1,2,&ast; Mengling Liu,1 Tianshu Liu1,2 1Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianshu Liu, Department of Medical Oncology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai, 20032, People’s Republic of China, Email liutianshu1969@126.comBackground: The highest incidence of human epidermal growth factor receptor 2 (HER2) mutations has been observed in bladder cancer (BC). However, the function of HER2 mutation in tumor progression and metastasis remains unclear. Currently, no responses to the pan-HER kinase inhibitor were observed in HER2-mutant BC.Case Presentation: We described a patient with metastatic bladder urothelial carcinoma (BUC) carrying a HER2 V842I mutation both in circulating tumor DNA (ctDNA) and biopsy sample. The patient was then treated with a HER2 tyrosine kinase inhibitor, pyrotinib, and responded well. However, the targeting treatment was terminated due to G3 diarrhea. Reduced dose of pyrotinib was later added to late-line treatment, the patient’s tumor again responded with a significant decrease in CA199.Conclusion: This is the first reported case of HER2 V842I mutation successfully treated with pyrotinib in BUC, suggesting pyrotinib therapy might serve as a therapeutic option for BUC patients harboring HER2 activating mutation.Keywords: bladder cancer, pyrotinib, V842I mutation, human epidermal growth factor receptor 2, next-generation sequencing

Ying Sun,1,2,&ast; Beibei Chen,3,4,&ast; Jisheng Li,3,&ast; Ling Peng,5 Shuguang Li,3 Xuejun Yu,3 Li Li3 1Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Pathology, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, 250012, People’s Republic of China; 2Department of Medical Oncology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, 266035, Shandong Province, People’s Republic of China; 3Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong Province, People’s Republic of China; 4Department of Radiation Oncology, Heze Municipal Hospital, Heze, 274031, Shandong Province, People’s Republic of China; 5Department of Respiratory Disease, Zhejiang Provincial People’s Hospital, Hangzhou, 310000, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Li; Xuejun YuDepartment of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Wenhua Xi Road 107, Jinan, 250012, Shandong Province, People’s Republic of ChinaTel +86 531-82169851Email drlili5060@163.com; yuxuejun@qiluhospital.comBackground: As a novel irreversible pan-ErbB inhibitor recently approved in China, pyrotinib has exhibited promising anticancer efficacy and acceptable safety profile in HER2-positive metastatic breast cancer (mBC). The aim of this retrospective study was to estimate the efficacy and safety of pyrotinib treatment in Chinese mBC patients.Methods: We retrospectively reviewed the real-world clinicopathological and treatment data of HER2-positive mBC patients receiving pyrotinib-based treatment from August 2018 to July 2019 in Qilu Hospital of Shandong University and other medical centers of Shandong Province in China.Results: A total of 64 patients treated with pyrotinib were included for analysis, and the median follow-up duration was 260 days (interquartile range, 199.0 to 339.0 days). Fifty-nine (92.2%) patients had been previously treated with trastuzumab and/or T-DM1, while 11 (17.2%) patients had been exposed to lapatinib. The objective response rate (ORR) of all patients was 73.4%, and the disease control rate (DCR) was 98.4%, with a clinical benefit rate (CBR) of 87.5%. Patients with exposure to lapatinib responded well to pyrotinib-based treatment, although the ORR was significantly lower compared with that of patients without exposure to lapatinib (44.1% vs 77.5%, p=0.037). Previous lapatinib exposure was negatively associated with the objective response of pyrotinib treatment (odds ratio [OR]=0.248, 95% confidence interval [CI] 0.063– 0.970, p=0.045). The median progression-free survival (mPFS) for patients with previous lapatinib exposure and patients with visceral metastasis was 299 days (95% CI 240.1– 357.9 days) and 359 days (95% CI 258.3– 459.7 days), respectively. But the mPFS of the whole cohort has not been reached until the cut-off date. Cox multivariate analysis revealed that only visceral metastasis was an independent predictor of significantly shorter PFS (p=0.041) but not previous exposure to lapatinib (p=0.092). Diarrhea (28.1%), hand-foot syndrome (17.2%), and neutropenia (9.4%) were the most common grade 3 adverse events associated with pyrotinib treatment.Conclusion: Pyrotinib is highly beneficial to HER2-positive metastatic breast cancer patients, even in patients with previous lapatinib exposure. Pyrotinib is a feasible replacement of lapatinib in combination with chemotherapeutic drugs or as a monotherapy. Adverse effects are tolerable and easily manageable.Keywords: breast cancer, HER2 positive, pyrotinib, adverse effect, objective response rate

Yueyue Liu, Qian Zhang, Chao Lu, Wei Hu Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of ChinaCorrespondence: Chao Lu; Wei HuDepartment of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of ChinaTel/Fax + 86-551 63806057Email 765385306@qq.com; huwei@ahmu.edu.cnPurpose: Pyrotinib, an irreversible human epidermal growth factor receptor 2 (HER2), is a epidermal growth factor receptor double-target tyrosine kinase inhibitor used for treating HER2-positive breast cancer. This study aimed to evaluate the impact of the strong CYP3A4 inhibitor itraconazole on the safety and pharmacokinetics of pyrotinib in Chinese healthy adults.Patients and Methods: This was an open-label, randomized, self-control study. Eighteen healthy adults were included in this trial. They received a single 80 mg dose of pyrotinib orally on days 1 and 9, and a 200 mg once-daily dose of itraconazole on days 6 through 22. Blood samples were obtained, and the drug concentration was detected using liquid chromatography/tandem mass spectrometry.Results: Compared with pyrotinib alone, the exposure to pyrotinib co-administered with itraconazole substantially increased, and the Cmax and AUC0-t increased by 2.78- and 10.8-fold, respectively. No serious adverse events were reported in this trial, and no participant dropped out of the trial because of adverse events.Conclusion: The exposure to pyrotinib was substantially affected by the action of itraconazole. The concomitant use of pyrotinib with itraconazole might require dose modification of pyrotinib. All treatments were well tolerated in healthy participants.Clinical Trial Registry: http://www.chinadrugtrials.org.cn/clinicaltrials.prosearch.dhtml, CTR20191866.Keywords: drug–drug interaction, itraconazole, pharmacokinetics, pyrotinib, safety

Yuzhen Yin,1 Hui Yang,2 Zhuo Liu,3 Jie Tan,2 Chunrong Zhu,4 Minbin Chen,5 Rengui Zhou,6 Lei Wang,7 Jun Qian2,8 1Department of Tumor Center, The Affiliated Jiangsu Shengze Hospital of Nanjing Medical University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Oncology, Suzhou Municipal Hospital, Suzhou, Jiangsu, People’s Republic of China; 3Department of Oncology, Zhangjiagang First People’s Hospital, Zhangjiagang, Jiangsu, People’s Republic of China; 4Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 5Department of Oncology, The First People’s Hospital of Kunshan, Kunshan, Jiangsu, People’s Republic of China; 6Department of Oncology, The 904th Hospital of the Joint Logistics Support Force of the Chinese People’s Liberation Army, Wuxi, Jiangsu, People’s Republic of China; 7Department of Breast Surgery, The First People’s Hospital of Changzhou, Changzhou, Jiangsu, People’s Republic of China; 8Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Jun QianDepartment of Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Qinhuai District, Nanjing, Jiangsu, People’s Republic of ChinaEmail junqian0415@126.comLei WangDepartment of Breast Surgery, The First People’s Hospital of Changzhou, No. 185, Juqian Street, Changzhou, Jiangsu, People’s Republic of ChinaEmail 592722409@qq.comBackground: Human epidermal growth factor receptor 2 (HER2) is a member of the ErbB family and is a key proto-oncogene in solid tumors. This pilot study investigated the safety and efficacy of pyrotinib in HER2-positive non-breast advanced solid tumors.Patients and Methods: Twenty-five patients with HER2-positive advanced solid tumors excluding breast cancer were enrolled to receive pyrotinib-based therapy. The primary end point was progression-free survival (PFS).Results: The median PFS and overall survival (OS) were 3.5 months (95% CI: 2.2– 5.0 months) and 9.6 months (95% CI: 4.4– 9.9 months), respectively. Ten patients with lung cancer and 9 patients with gastric cancer had a median PFS of 2.5 months (95% CI: 0.97– 6.53 months) and 2.9 months (95% CI: 1.50– 7.17 months), respectively. The median OS was 9.9 months (95% CI: 4.4– 9.9 months) in patients with lung cancer and 5.9 months (95% CI: 4.0– 9.6 months) in patients with gastric cancer. No statistical significance of a median OS was observed, nonetheless, patients receiving > 3 lines had a numerically lower median OS than those receiving ≤ 3 lines of treatment (9.9 vs 5.1 months, P = 0.706). All 23 patients were available for efficacy evaluation. The objective response rate (ORR) was 52.17% and disease control rate (DCR) was 91.3%. The ORR for lung cancer was 44.4% and for gastric cancer was 50%. In addition, the DCR for lung cancer was 77.8% and for stomach cancer was 100%. Moreover, patients receiving ≤ 3 lines of treatment had a numerically higher DCR than those receiving > 3 lines of treatment (94.1% vs 83.3%, P = 0.462). The most common treatment-related adverse events (TRAEs) were diarrhea (92%), but only 5 (20%) patients reported grade 3 diarrhea which could be well controlled.Conclusion: Pyrotinib-based therapy demonstrates promising efficacy for HER2-positive advanced solid tumors excluding breast cancer and toxicities could be well controlled. The study is a pilot study motivating larger studies to elucidate the safety and efficacy of pyrotinib in non-breast solid tumors.Keywords: pyrotinib, HER2-positive, solid tumor