title: A single-arm phase II trial of first-line paclitaxel in combination with lapatinib in HER2-overexpressing metastatic breast cancer.
abstract: BACKGROUND
  Lapatinib, an orally active tyrosine kinase inhibitor of epidermal growth factor receptor ErbB1 (EGFR) and ErbB2 (HER2), has activity as monotherapy and in combination with chemotherapy in HER2-overexpressing metastatic breast cancer (MBC).
  
  
  METHODS
  This phase II single-arm trial assessed the safety and efficacy of first-line lapatinib in combination with paclitaxel in previously untreated patients with HER2-overexpressing MBC. The primary endpoint was the overall response rate (ORR). Secondary endpoints were the duration of response (DoR), time to response, time to progression, progression-free survival (PFS), overall survival, and the incidence and severity of adverse events. All endpoints were investigator- and independent review committee (IRC)-assessed.
  
  
  RESULTS
  The IRC-assessed ORR was 51% (29/57 patients with complete or partial response) while the investigator-assessed ORR was 77% (44/57). As per the IRC, the median DoR was 39.7 weeks, and the median PFS was 47.9 weeks. The most common toxicities were diarrhea (56%), neutropenia (44%), rash (40%), fatigue (25%), and peripheral sensory neuropathy (25%).
  
  
  CONCLUSIONS
  First-line lapatinib plus paclitaxel for HER2-overexpressing MBC produced an encouraging ORR with manageable toxicities. This combination may be useful in first-line treatment for patients with HER2-overexpressing MBC and supports the ongoing evaluation of this combination as first-line therapy in HER2-overexpressing MBC.
authors.affiliation: Nzoz Onko-Med, Wieliszew, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Jagiello-Gruszfeld
authors.forename: Sergei
authors.initials: S
authors.lastname: Tjulandin
authors.forename: Natalya
authors.initials: N
authors.lastname: Dobrovolskaya
authors.forename: Alexey
authors.initials: A
authors.lastname: Manikhas
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Pienkowski
authors.forename: Michelle
authors.initials: M
authors.lastname: DeSilvio
authors.forename: Mona
authors.initials: M
authors.lastname: Ridderheim
authors.forename: Rowena
authors.initials: R
authors.lastname: Abbey
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077341:Lapatinib; D007844:Latvia; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D011044:Poland; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012383:Romania; D012426:Russia; D015854:Up-Regulation
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D000077341:Lapatinib; D017239:Paclitaxel; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone