Lapatax: a phase I study of neoadjuvant lapatinib combined with docetaxel in Her2/neu overexpressing breast cancer (BC). EORTC protocol 10054.

Abstract

Abstract Abstract #5112 Background: Lapatinib (L) has been shown to be an effective anti-HER2 therapy in advanced breast cancer, and is under study as an adjuvant therapy in the ALTTO and TEACH studies. Whilst there are ongoing neoadjuvant studies with the combination of Lapatinib and paclitaxel, there are none with docetaxel (D), considered by many to be the most active taxane in breast cancer, mainly due to the limited data available on the safety and efficacy of this combination. Hence there is a need for this dose-finding study which is being conducted as a prelude to a randomized phase II trial.
 Objective: The objectives are to establish the maximum tolerated dose (MTD), to characterize Dose limiting toxicity (DLT) and to define the recommended dose for phase II.
 Patients and Methods: Female patients (pts) with locally advanced, inflammatory or large operable BC are treated with escalating doses of L from 1000 to 1250 mg/d, administered orally once daily continuously in combination with D given every 21 days at dose ranges of 75 to 100 mg/m² for 4 cycles. At least three pts are treated at each dose level (DL). DLT is defined during cycle 1: any grade 3-4 non hematological toxicity, ANC<0.5 G/L lasting for 7days or more, Febrile neutopenia or thrombocytopenia <25 G/L. Growth factors are given only in case of clinical symptoms. Core biopsies are mandatory at baseline and after cycle 4. Pharmacokinetic samples are collected on day 1 of cycles 1 and 2.
 Results: As of June 10, 10 pts with a median age of 56 years (range 17-64) were enrolled and 3 DLs (DL 3: L 1000 mg/day, D: 85 mg/m²) have been fully investigated. No pt had a DLT during cycle 1. The toxicity profile for 30 documented cycles is summarized in this table.
 
 The 4th cycles LVEF has been documented in 4 patients, one of whom had a drop by 16% to a value of 55%.
 Conclusions: The toxicity of docetaxel-lapatinib during the first 3 dose levels is excellent. Final toxicity data and PK results of this phase 1 will be presented at the meeting. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5112.