title: Final results of a multicenter phase II clinical trial evaluating the activity of single-agent lapatinib in patients with HER2-negative metastatic breast cancer and HER2-positive circulating tumor cells. A proof-of-concept study.
abstract: This multicenter phase II trial was designed to evaluate the activity of lapatinib in metastatic breast cancer patients with HER2-negative primary tumors and HER2-positive circulating tumor cells (CTCs). In this study MBC patients with HER2-negative primary tumors and HER2-positive CTCs previously treated with at least a first-line therapy for metastatic disease received lapatinib 1500 mg/day. The CellSearch System® was used for CTCs isolation and bio-characterization. HER2 status was assessed on CTCs by immunofluorescence. A case was defined as CTCs positive if ≥2 CTC/7.5 ml of blood were isolated and HER2-positive if ≥50% of CTCs were HER2-positive. 139 HER2-negative patients were screened, 96 patients were positive for CTCs (mean number of CTCs: 85; median number of CTCs: 19; range 2-1637). Seven of the 96 patients (7%) had ≥50% HER2-positive CTCs and were eligible for treatment with lapatinib. No objective tumor responses occurred in this population. In one patient, disease stabilization lasting 254 days (8.5 months) was observed. From the findings of this study, we concluded that a subset of patients with a HER2-negative primary tumor presents HER2-positive CTCs during disease progression, although the HER2 shift rate seems to be lower than previously reported. Despite the lack of objective response, the durable disease stabilization observed in one patient cannot rule out the hypothesis that lapatinib may have some activity in this patient population. However, considering that only 1/139 screened patients may potentially have derived benefit from this approach, future trials designed according to the presented strategy cannot be recommended.
authors.affiliation: Medical Oncology Unit, Hospital of Prato, Prato, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Pestrin
authors.forename: Silvia
authors.initials: S
authors.lastname: Bessi
authors.forename: Fabio
authors.initials: F
authors.lastname: Puglisi
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Minisini
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masci
authors.forename: Nicola
authors.initials: N
authors.lastname: Battelli
authors.forename: Alberto
authors.initials: A
authors.lastname: Ravaioli
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Gianni
authors.forename: Roberta
authors.initials: R
authors.lastname: Di Marsico
authors.forename: Carlo
authors.initials: C
authors.lastname: Tondini
authors.forename: Stefania
authors.initials: S
authors.lastname: Gori
authors.forename: Charles R
authors.initials: CR
authors.lastname: Coombes
authors.forename: Justin
authors.initials: J
authors.lastname: Stebbing
authors.forename: Laura
authors.initials: L
authors.lastname: Biganzoli
authors.forename: Marc
authors.initials: M
authors.lastname: Buyse
authors.forename: Angelo
authors.initials: A
authors.lastname: Di Leo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D018275:Carcinoma, Lobular / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human