演題抄録

International Session(Poster)

開催概要
開催回
第51回・2013年・京都
 

Pharmacokinetics and safety of pertuzumab in HER2-positive gastric cancer

演題番号 : ISP-14

[筆頭演者]
Yoon-Koo Kang:1 
[共同演者]
Sun Young Rha:2、Pierfrancesco Tassone:3、Jorge Barriuso:4、Ron Yu:5、Tania Szado:5、Amit Garg:5、Yung-Jue Bang:6

1:Asan Medical Center, University of Ulsan, Korea、2:Yonsei Cancer Center, Yonsei University College of Medicine, Korea、3:Medical Oncology Unit, Magna Graecia University, Italy、4:Hospital Universitario La Paz, Spain、5:Genentech, USA、6:Seoul National University Hospital, Korea

 

Background: HER2 is overexpressed in 15-20% of advanced gastric (aGC) or gastroesophageal junction (GEJ) cancer, where trastuzumab (T)+chemotherapy (CX) significantly improved overall survival compared with CX. Pertuzumab (P)+T+docetaxel significantly improved progression-free and overall survival compared with T+docetaxel in HER2-positive first-line (1L) metastatic breast cancer. P+T+CX has the potential to improve survival outcomes in HER2-positive aGC. We therefore conducted a Phase IIa study of the pharmacokinetics (PK) and safety of P+T+CX in HER2-positive inoperable locally advanced or recurrent and/or metastatic adenocarcinoma of the stomach or GEJ. Methods: JOSHUA was a randomized, open-label, multicenter study of two different doses of P in 1L treatment of HER2-positive aGC or GEJ cancer. Patients (pts) received P 840 mg for Cycle 1 and 420 mg for Cycles 2-6 q3w (Arm A) or P 840 mg Cycles 1-6 q3w (Arm B). 6 cycles of T, cisplatin and capecitabine were also given, followed by T q3w until disease progression or unmanageable toxicity. Primary endpoints were P trough concentrations (Cmin) at Day 43 (to identify the P dose giving a steady-state Cmin of ≧20ug/mL in ≧90% of pts) and safety. Results: 15 pts were randomized to each arm. Mean Cmin at Day 43 in Arms A and B was 40.0ug/mL (CV 43.2%) and 57.9ug/mL (CV 56.5%), respectively, and the estimated proportion of pts achieving the target Cmin was Arm A: 91.6% (95% CI 78.3-99.2) and Arm B: 98.3% (95% CI 91.4-99.97). At this interim safety assessment, there was no overall difference in the adverse event (AE) profile between arms. The most common grade ≧3 AEs (≧4 pts overall) were diarrhea, neutropenia, anemia, decreased appetite, fatigue, febrile neutropenia, hyponatremia, and stomatitis. Preliminary efficacy data will be presented. Conclusions: Based on these PK and safety data, the higher dose of P (840 mg q3w) was selected for a Phase III study of P+T+CX in 1L HER2-positive aGC or GEJ cancer (NCT01774786).

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