WEI-WU CHENYeh D.-C.Chao T.-Y.CHING-HUNG LINChow L.W.-C.DWANG-YING CHANGHsieh Y.-Y.Huang S.-M.ANN-LII CHENGYEN-SHEN LUTaiwan Breast Cancer Consortium2020-05-252020-05-2520180368-2811https://www.scopus.com/inward/record.uri?eid=2-s2.0-85043471928&doi=10.1093%2fjjco%2fhyx188&partnerID=40&md5=efa7e9191737216afc890cfbd6aff4adhttps://scholars.lib.ntu.edu.tw/handle/123456789/494553Background: The combination of lapatinib and oral vinorelbine for HER2 positive metastatic breast cancer (MBC) is convenient but with uncertain toxicity profiles. A Phase I/II study was designed to understand the tolerability and efficacy of this combination treatment. Method: Female MBC patients with HER2 positive were eligible. Lapatinib was given once daily and oral vinorelbine was given on Days 1 and 8 of a 21-day cycle. A 3 + 3 standard dose-escalation rule was applied in the Phase I study. The primary endpoint of the Phase II study was PFS. In the Phase II part, because no DLT was observed in the first 20 patients, vinorelbine dose-escalation was permitted if no significant toxicities after the first cycle was observed. Result: From June 2009 to February 2013, 46 patients were enrolled in Phase I (n = 15) and II (n = 31) studies. Median age was 52.8 (range 34.3-84.0); 28 (60.9%) patients were ER positive. In the Phase I study, two patients had DLTs (neutropenia (n = 2), diarrhea (n = 1)). The MTD was determined at lapatinib 1000 mg plus oral vinorelbine 50 mg/m2. In the Phase II study, 11 patients safely had vinorelbine escalated to 60 mg/m2 on cycle 2. The median PFS was 5.6 months (95% CI 5.2-5.9); 6 (19.4%) patients had PR; the clinical benefit rate was 38.7%. Six patients had disease control over 2 years. Conclusion: Lapatinib 1000 mg and oral vinorelbine 50 mg/m2 were tolerable with manageable toxicities. Escalation to vinorelbine 60 mg/m2 is feasible if no significant toxicities after the first cycle. Clinical efficacy was demonstrated with long-term responders observed. ? The Author(s) 2018. Published by Oxford University Press. All rights reserved.[SDGs]SDG3lapatinib; vinorelbine tartrate; antineoplastic agent; epidermal growth factor receptor 2; ERBB2 protein, human; lapatinib; quinazoline derivative; vinblastine; vinorelbine tartrate; adult; age; Article; cancer combination chemotherapy; cancer control; clinical article; diarrhea; drug dose escalation; drug efficacy; drug response; drug safety; drug tolerability; estrogen receptor positive breast cancer; female; human; human epidermal growth factor receptor 2 positive breast cancer; multiple cycle treatment; neutropenia; phase 1 clinical trial; phase 2 clinical trial; progression free survival; aged; analogs and derivatives; breast tumor; clinical trial; demography; disease free survival; dose response; metabolism; metastasis; middle aged; oral drug administration; pathology; treatment outcome; very elderly; Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Demography; Disease-Free Survival; Dose-Response Relationship, Drug; Female; Humans; Middle Aged; Neoplasm Metastasis; Quinazolines; Receptor, ErbB-2; Treatment Outcome; Vinblastinejournal article10.1093/jjco/hyx188293153942-s2.0-85043471928