Phase Ib dose-finding trial of lapatinib plus pegylated liposomal doxorubicin in advanced HER2-positive breast cancer

Andrea Rocca, Lorenzo Cecconetto, Alessandro Passardi, Elisabetta Melegari, Daniele Andreis, Manuela Monti, Roberta Maltoni, Samanta Sarti, Elisabetta Pietri, Alessio Schirone, Francesco Fabbri, Caterina Donati, Oriana Nanni, Anna Fedeli, Marina Faedi, Dino Amadori

Research output: Contribution to journalArticlepeer-review


Purpose: Combination of anthracyclines with trastuzumab is hampered by cardiotoxicity. Pegylated liposomal doxorubicin and lapatinib could represent a safer alternative to combination therapy. Methods: In 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. Results: Nine 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. Conclusions: Combination of pegylated liposomal doxorubicin and lapatinib is feasible and potentially active in pretreated HER2-positive advanced breast cancer patients. Trial registration: NCT02131506 ( identifier).

Original languageEnglish
Pages (from-to)863-871
Number of pages9
JournalCancer Chemotherapy and Pharmacology
Issue number5
Publication statusPublished - May 1 2017


  • Breast cancer
  • HER2
  • Lapatinib
  • Pegylated liposomal doxorubicin
  • Phase Ib
  • Targeted therapy

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)


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