演題抄録

一般演題(口演)

開催概要
開催回
第51回・2013年・京都
 

A Phase 1b Trial of Trastuzumab Emtansine in Combination with Pertuzumab

演題番号 : O10-5

[筆頭演者]
Hiroji Iwata:1 
[共同演者]
Jun Horiguchi:2、Nobuaki Sato:3、Mari Matsubara:5、Kanatani Kazumitsu :5、Yasuhiro Fujiwara:4

1:Breast Oncology, Aichi Cancer Center, Japan、2:Department of Breast and Endocrine Surgery, Gunma University Hospital, Japan、3:Breast Surgery, Niigata Cancer Center Hospital, Japan、4:Department of Breast and Medical Oncology, National Cancer Center Hospital, Japan、5:Chugai Pharmaceutical Co. Ltd, Japan

 

BackgroundTrastuzumab emtansine (T-DM1) is an antibody-drug conjugate composed of trastuzumab, a stable linker, and DM1 (a microtubule inhibitor). EMILIA, a pivotal phase 3 study of T-DM1 in patients with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab and a taxane, met both co-primary efficacy endpoints of progression-free survival and overall survival (Verma, NEJM 2012). In a phase 1b/2 study, the combination of T-DM1 and pertuzumab (a HER2 dimerisation inhibitor) was shown to have an encouraging safety and efficacy profile in non-Japanese patients with HER2-positive MBC previously treated with trastuzumab (Miller, ASCO 2010). Here we report the tolerability and safety of this combination in Japanese patients.MethodsJO22992 is a phase Ib, multicenter, single-arm trial in Japanese patients with HER2-positive MBC. Patients received T-DM1 (3.6 mg/kg) with full-dose pertuzumab (840 mg loading dose, then 420 mg maintenance dose) given every 3 weeks until progression disease or unacceptable toxicity. Key eligibility criteria were ECOG PS of 0 to 2 and prior treatment with trastuzumab and chemotherapy. The primary endpoints were tolerability and pharmacokinetics; the secondary endpoint was tumor response. ResultsSix patients were enrolled. Median age was 57.5 years (range, 46-68). Median duration of treatment was 11 cycles (range, 1-32). Grade>3 adverse events (AEs) were increased AST, decreased LVEF and neutropenia (n=1 each). Grade3 decreased LVEF occurred at cycle1 led to discontinuation, but recovered within 30 days. Two serious AEs occurred in 1 patient each: hemorrhagic gastric ulcer and epistaxis. The pharmacokinetic parameters of each drug were similar to those seen in single-agent trials. Overall response rate was 50%.ConclusionThe combination of T-DM1 with pertuzumab has encouraging tolerability in Japanese patients with HER2-positive MBC; these results warrant further evaluation in this patient population.

キーワード

臓器別:乳腺

手法別:臨床試験

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