title: A phase II study of afatinib, an irreversible ErbB family blocker, added to letrozole in patients with estrogen receptor-positive hormone-refractory metastatic breast cancer progressing on letrozole.
abstract: Phase II, open-label study assessing the efficacy and safety of the ErbB family blocker afatinib combined with letrozole in estrogen receptor-positive metastatic breast cancer (MBC) patients who had progressed on letrozole monotherapy. Adult females (N = 28) received oral afatinib (50 [n = 7], 40 [n = 13] or 30 [n = 8] mg/day) plus letrozole 2.5 mg/day in 28-day cycles until disease progression. Primary endpoint was the progression-free rate at or after 16 weeks of afatinib. At 16 weeks, four patients remained on afatinib without progression; two of these were HER2 negative. Fifteen (54 %) patients had a best response of stable disease according to Response Evaluation Criteria in Solid Tumors. Median progression-free survival was 60, 107 and 79 days with 50, 40 and 30 mg/day afatinib, respectively. Diarrhea, asthenia, rash, mucosal inflammation and nausea were the most frequent adverse events. In this small, exploratory study, afatinib combined with letrozole was able to induce disease stabilization in 54 % of hormone-refractory MBC patients previously progressing on letrozole.
  
  
  BACKGROUND
  NCT00708214.
authors.affiliation: Oncologue-Service de Recherche Clinique, Centre François Baclesse, Avenue Général Harris, 14076 Caen Cedex 05, France.
authors.forename: Katharina
authors.initials: K
authors.lastname: Gunzer
authors.affiliation: Oncologue-Service de Recherche Clinique, Centre François Baclesse, Avenue Général Harris, 14076 Caen Cedex 05, France ; Centre Hospitalier Universitaire Côte de Nacre, Caen, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Joly
authors.affiliation: Centre Antoine Lacassagne, Nice, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Ferrero
authors.affiliation: APHP, HUEP-Tenon Hospital, Paris, France ; Institut Universitaire de Cancérologie, UPMC, Paris, France.
authors.forename: Joseph
authors.initials: J
authors.lastname: Gligorov
authors.affiliation: Boehringer Ingelheim France S.A.S., Reims, France.
authors.forename: Helene
authors.initials: H
authors.lastname: de Mont-Serrat
authors.affiliation: Boehringer Ingelheim Pharma GmbH and Co. KG, Biberach, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Uttenreuther-Fischer
authors.affiliation: Boehringer Ingelheim Ltd., Bracknell, UK.
authors.forename: Katy
authors.initials: K
authors.lastname: Pelling
authors.affiliation: Boehringer Ingelheim Pharma GmbH and Co. KG, Biberach, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Wind
authors.affiliation: Hôpital Saint Louis, Paris, France.
authors.forename: Guilhem
authors.initials: G
authors.lastname: Bousquet
authors.affiliation: Hôpital Saint Louis, Paris, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Misset
keywords: Afatinib; ErbB Family Blocker; Letrozole; Metastatic breast cancer; Pharmacokinetics; Phase II
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