title: Phase II study assessing lapatinib added to letrozole in patients with progressive disease under aromatase inhibitor in metastatic breast cancer-Study BES 06.
abstract: This trial evaluated the effect of adding lapatinib to letrozole after clinical resistance to aromatase inhibitor (IA) treatment in hormone receptor-positive metastatic breast cancer. Postmenopausal women received daily letrozole plus lapatinib (1,500 mg). The primary end point was objective rate response (ORR) at week 12. Secondary objectives included time to response, duration of response, clinical benefit (CB), progression-free survival (PFS), overall survival, and safety. Twenty-four human epidermal growth factor receptor 2 (HER2)-negative patients were included with secondary resistance to IA. ORR at 12 weeks was 4 % (95 % confidence interval (CI), 0.7-20). Stable and progression diseases were reported in 25 % (95 % CI, 12-45) and 71 % (95 % CI, 51-85) of cases, respectively. At 24 weeks, the ORR increased to 8 %. CB was 21 % (95 % CI, 9-40). At a median follow-up of 27 months, median PFS was 3.4 months (95 % CI, 2.8-5.4). Grade 3 or 4 adverse events were rarely reported. No clinical cardiac toxicity was observed. Lapatinib was discontinued in two patients due to severe diarrhea. This trial was prematurely closed due to low recruitment. These preliminary results suggest that the addition of lapatinib to letrozole has a favorable safety profile and could overcome tumoral resistance to letrozole among HER2-negative tumors.
authors.affiliation: Centre Hospitalier Universitaire de Besançon, Besançon, France. cvillanueva@chu-besancon.fr
authors.forename: C
authors.initials: C
authors.lastname: Villanueva
authors.forename: G
authors.initials: G
authors.lastname: Romieu
authors.forename: J
authors.initials: J
authors.lastname: Salvat
authors.forename: L
authors.initials: L
authors.lastname: Chaigneau
authors.forename: Y
authors.initials: Y
authors.lastname: Merrouche
authors.forename: T
authors.initials: T
authors.lastname: N'guyen
authors.forename: A Thiery
authors.initials: AT
authors.lastname: Vuillemin
authors.forename: M
authors.initials: M
authors.lastname: Demarchi
authors.forename: E
authors.initials: E
authors.lastname: Dobi
authors.forename: Xavier
authors.initials: X
authors.lastname: Pivot
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D000077341:Lapatinib; D000077289:Letrozole; D008875:Middle Aged; D060787:Neoplasm Grading; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D047072:Aromatase Inhibitors; D066246:ErbB Receptors; D000077341:Lapatinib; D000077289:Letrozole; D009570:Nitriles; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D014230:Triazoles