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A multicenter trial evaluating retaspimycin HCL (IPI-504) plus trastuzumab in patients with advanced or metastatic HER2-positive breast cancer.

Abstract：

:Heat shock protein 90 (Hsp90) facilitates maturation and stability of HER2. Combining an Hsp90 inhibitor and trastuzumab has demonstrated anti-tumor effects in patients with HER2+ breast cancer. Adults with measurable, locally advanced or metastatic HER2+ breast cancer and prior trastuzumab treatment were enrolled in a phase 2 trial employing weekly 300 mg/m(2) retaspimycin HCl, a potent Hsp90 inhibitor, with 6 mg/kg trastuzumab every 3 weeks. A Simon's two-stage design determined trial expansion by dose-limiting toxicity (DLT) and response rates. Pharmacokinetics and electrocardiograms were evaluated. Twenty-six patients with median age 52.5 years (range 33-72) enrolled with a median of six prior chemotherapeutic regimens (range 2-20). On study, patients received a median of three treatment cycles (range 1-12). No DLTs were observed. Most adverse events (AEs) were grade 1 or 2; common treatment-related AEs included fatigue (46 %), nausea (31 %), and diarrhea (23 %). One patient had treatment-related serious AEs of grade 1 diarrhea and grade 3 hypokalemia. grade 3 transaminase elevation occurred in one patient (4 %) who also had metastatic liver disease. Sixteen patients (62 %) had stable disease, with a median on-study duration of 2.4 months (range 1.1-8.2). No confirmed responses were observed. Retaspimycin HCl at 300 mg/m² weekly in combination with trastuzumab was well tolerated and without significant toxicities. Modest clinical activity was observed, but did not meet criteria for trial expansion. The safety profile for patients on study raises the possibility of retaspimycin HCl underdosing that limited efficacy. Studies employing higher doses are ongoing.

journal_name

Breast Cancer Res Treat

journal_title

Breast cancer research and treatment

authors

Modi S,Saura C,Henderson C,Lin NU,Mahtani R,Goddard J,Rodenas E,Hudis C,O'Shaughnessy J,Baselga J

doi

10.1007/s10549-013-2510-5

subject

Has Abstract

pub_date

2013-05-01 00:00:00

pages

107-13

issue

eissn

0167-6806

issn

1573-7217

journal_volume

139

pub_type

杂志文章,多中心研究

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A multicenter trial evaluating retaspimycin HCL (IPI-504) plus trastuzumab in patients with advanced or metastatic HER2-positive breast cancer.