e11529 Background: Previous studies evidenced that the combination docetaxel (D) (75 mg/m²) + lapatinib (L) (1,250 mg/d) is well tolerated in heavily pretreated HER2-positive metastatic breast cancer patients (pts) in association with systematic G-CSF. This phase I study was conducted to assess safety, optimal tolerated regimen (OTR) and clinical activity of D + L in naïve treatment pts with HER-2 positive LAMBC without primary use of growth factor. Methods: Women with HER2+ LAMBC, naïve of treatment for advanced or metastatic disease, ECOG PS 0-2, were eligible for this study. Pts received once daily oral dosing of L with intravenous D on day 1 of every 3 week cycle. Initial dose was D (75 mg/m²) + L (1,250 mg/d) escalating up to D 100 mg/m² and L 1,500 mg/d until the Maximal Tolerated Dose (MTD) was reached. An expansion cohort of 6 pts was treated at the OTR level. Primary use of G-CSF was not permitted. Results: From Aug 2008 to Nov 2011, 17 pts were enrolled: median age 54.4 years [34.6-77], 59% were PS 0. All patients have metastatic disease with lung (29,4%), bone (41,2%), liver (76.5%) and lymph nodes (35.3%) metastasis. 7 pts received previously chemotherapy in adjuvant setting, 5 pts hormonotherapy and 7 pts radiotherapy. All but two pts were evaluable for dose limiting toxicities (DLT). 1 DLT/6 pts (FN) was observed at dose level (DL) 1 (D 75 mg/m² + L 1,250 mg/d) and 2 DLT/3 pts (gr 3 diarrhoea; gr4 neutropenia >7 d) at DL2 (D 75 mg/m² + L 1,500 mg/d). Only one DLT (FN) was observed in expansion cohort at OTR (D 75 mg/m² + L 1,250 mg/d; 6 pts). Over all C1, other significant toxicities (% pts) included gr4 neutropenia 53%, gr3 transaminase increase 6%, gr2 skin rash 36%, gr2 nausea/vomiting 18%, gr2 diarrhoea 12%, gr2 stomatitis 12%, gr2 hand-foot syndrome 6%; no decrease of cardiac function occurred. Conclusions: OTR for D and L was 75 mg/m² once every 3 weeks and 1,250 mg once daily respectively. This study demonstrates that this combination could be administered without systematic use of G-CSF in non pretreated pts with LAMBC. Additional safety data and preliminary evidence of activity are anticipated to be available at the time of presentation. Clinical trial information: NCT01044485.
Phase I and pharmacokinetic study of trastuzumab emtansine in Japanese patients with HER2-positive metastatic breast cancer