Abstract
PurposeCombination of anthracyclines with trastuzumab is hampered by cardiotoxicity. Pegylated liposomal doxorubicin and lapatinib could represent a safer alternative to combination therapy.MethodsIn this phase Ib study with 3 + 3 dose escalation design, patients with HER2-positive advanced breast cancer received pegylated liposomal doxorubicin 30 mg/m2 intravenously on day 1 plus lapatinib 1250 (level 1) or 1500 (level 2) mg/day orally on days 1–21 of each 21-day cycle. The aims were to establish the maximum tolerated dose at first cycle, and the activity and safety of multiple cycles.ResultsNine patients out of 11 enrolled were evaluable: 3 at level 1 and 6 at level 2. No dose-limiting toxicities occurred at dose level 1, while 1 (grade 3 diarrhea) occurred at dose level 2, leading to the expansion of this cohort to 6 patients, with no further dose-limiting toxicities. Main grade 1–2 toxicities at first cycle were leucopenia, diarrhea, elevated transaminases, mucositis. Three patients had grade 3 toxicities at subsequent cycles, including colitis, anorexia, stomatitis plus hand-foot syndrome. One partial response, 5 disease stabilizations, and 3 disease progressions were reported.ConclusionsCombination of pegylated liposomal doxorubicin and lapatinib is feasible and potentially active in pretreated HER2-positive advanced breast cancer patients.Trial registrationNCT02131506 (ClinicalTrials.gov identifier).
Highlights
IntroductionBefore the advent of anti-human epidermal growth factor receptor 2 (HER2) therapies, survival of metastatic HER2-positive Breast cancer (BC) patients was quite poor [3]
Breast cancer (BC), the most frequent cancer worldwide among women, and one of the main leading causes of cancer death [1], consists of different subtypes according to biology, prognosis, and treatment response [2].Before the advent of anti-human epidermal growth factor receptor 2 (HER2) therapies, survival of metastatic HER2-positive BC patients was quite poor [3]
Evidence of benefit from HER2-targeted therapies beyond second-line treatment of metastatic BC is not definitive [6], its use is common in clinical practice and is recommended by treatment guidelines [7]
Summary
Before the advent of anti-human epidermal growth factor receptor 2 (HER2) therapies, survival of metastatic HER2-positive BC patients was quite poor [3]. The advent of targeted therapies has led to impressive improvements in survival [4]. Long-term outcome data show that only about 12% of patients maintains disease remission after 5 years of first-line trastuzumab-based therapy [5], and almost all patients eventually undergo disease progression and require additional therapies. Evidence of benefit from HER2-targeted therapies beyond second-line treatment of metastatic BC is not definitive [6], its use is common in clinical practice and is recommended by treatment guidelines [7]. Anthracyclines are among the most active drugs in BC [8], and have been hypothesized [9] to be effective in HER2-positive tumors [10].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
