演題抄録

一般演題(口演)

開催概要
開催回
第51回・2013年・京都
 

P2 Study of Two PI3K/mTOR Inhibitors in Endometrial Ca. - Japan Lead-in-Cohort

演題番号 : O138-5

[筆頭演者]
Kei Muro:1 
[共同演者]
Koji Matsumoto:2、Yasuhiro Fujiwara:3、Lixin Han:4、Kosei Hasegawa:5、Satoshi Hashigaki:6、Toru Nakanishi:7、Kiyoshi Fujiwara:8、Mayu Yunokawa:3、Tomoko Hirohashi:6、Brett Houk:4、Robert Millham:4、Mie Suzuki:6、Jennifer Vermette:4、Keiichi Fujiwara:5

1:Department of Clinical Oncology, Aichi Cancer Center Hospital, Japan、2:Department of Medical Oncology, Hyogo Cancer Center, Japan、3:Department of Breast Oncology and Medical Oncology, National Cancer Center Hospital, Japan、4:Pfizer Inc., USA、5:Department of Gynecologic Oncology, Saitama International Medical Center, Saitama Medical Universtiy, Japan、6:Pfizer Japan Inc., Japan、7:Department of Gynecologic Oncology, Aichi Cancer Center Hospital, Japan、8:Department of Gynecologic Oncology, Hyogo Cancer Center, Japan

 

Background: PF-04691502 (PF-502) and PF-05212384 (PF-384) are potent PI3K/mTOR dual inhibitors having different chemical structures, intended for daily oral and weekly IV dosing, respectively. B1271004 (1004) is an ongoing P2, randomized, open-label, non-comparative, multinational study in recurrent EC. In Western (W) pts, the MTD of PF-502 is 8 mg QD and for PF-384 is 154 mg Qw. Since 1004 is the first in Japanese (J) study, the lead in cohort (LIC) of J-pts was enrolled prior to the P2 part to confirm safety.Materials and Methods: The LIC included 3 treatment arms; PF-502 4 mg/day (Arm A), PF-384 89 mg/wk (Arm B) and PF-384 154 mg (Arm C), given as single agents in J-pts with recurrent EC. The purpose of the LIC is to investigate whether there is significant difference btw J- and W-pts on the safety and PK. Results: Overall, 9 pts were enrolled into the LIC. 3 pts were enrolled to each Arms (Arm A, B and C). Mean age (y) in Arm A was 64 (61-70), in Arm B was 56 (40-69) and in Arm C was 62 (57-71); Median treatment duration (day) for Arm A was 70 (28-84), Arm B was 330 (29-337), and Arm C was 60 (50-77). As of data cutoff, all but 3 pts (2 in Arm B and 1 in Arm C) had discontinued from the study; 4 from PD (1 in Arm A, 1 in Arm B, 2 in Arm C), and 2 due to AE (both in Arm A). Most common drug-related AEs (each 100%) for Arm A were hyperglycemia and rash, nausea and mucositis for Arm B and mucositis and sore throat for Arm C. 1 pt (Arm A) experienced a drug related SAE (pneumoncystis pneumonia). 1 pt (Arm C) had a dose reduction. Discussion: In J-pts, PF-384 was well tolerated at both doses (89 mg and 154 mg). In contrast, PF-502 was not well tolerated in J-pts, with 2 out of 3 pts discontinuing due to AEs. Due to safety issues in W- and J-pts, the global clinical development of PF-502 has been discontinued. The LIC was effective in its goal to evaluate safety and PK in J-pts, and they are currently being enrolled into the P2 part of 1004 to be treated with PF-384.

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