A phase 2 clinical trial of the heat shock protein 90 (HSP 90) inhibitor ganetespib in patients with refractory advanced
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PHASE II STUDIES
A phase 2 clinical trial of the heat shock protein 90 (HSP 90) inhibitor ganetespib in patients with refractory advanced esophagogastric cancer Lipika Goyal 1,2 & Surendra Pal Chaudhary 1,2 & Eunice L. Kwak 1,2 & Thomas A. Abrams 1,3 & Amanda N. Carpenter 2 & Brian M. Wolpin 1,3 & Raymond C. Wadlow 4 & Jill N. Allen 1,2 & Rebecca Heist 1,2 & Nadine Jackson McCleary 1,3 & Jennifer A. Chan 1,3 & Wolfram Goessling 1,3 & Deborah Schrag 1,3 & Kimmie Ng 1,3 & Peter C. Enzinger 1,3 & David P. Ryan 1,2 & Jeffrey W. Clark 1,2 Received: 13 November 2019 / Accepted: 19 December 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Summary Subsets of esophagogastric (EG) cancers harbor genetic abnormalities, including amplification of HER2, MET, or FGFR2 or mutations in PIK3CA, EGFR, or BRAF. Ganetespib which is a novel triazolone heterocyclic inhibitor of HSP90, is a potentially biologically rational treatment strategy for advanced EG cancers with these gene amplification. This multicenter, single-arm phase 2 trial enrolled patients with histologically confirmed advanced EG cancer with progression on at least one line of systemic therapy. Patients received Ganetespib 200 mg/m2 IV on Days 1, 8, and 15 of a 28-day cycle. The primary endpoint was overall response rate (ORR). Secondary endpoints included: Progression Free Survival (PFS); to correlate the presence of HSP clients with ORR and PFS; evaluating the safety, tolerability and adverse events profile. In this study 26 eligible patients mainly: male 77%, median age 64 years were enrolled. The most common drug-related adverse events were diarrhea (77%), fatigue (65%), elevated ALKP (42%), and elevated AST (38%). The most common grade 3/4 AEs included: leucopenia (12%), fatigue (12%), diarrhea (8%), and elevated ALKP (8%). The ORR of 4% reflects the single patient of 26 who had a complete response and stayed on treatment for more than seventy (70) months. Median PFS and OS was 61 days (2.0 months), 94 days (3.1 months) respectively. Ganetespib showed manageable toxicity. While the study was terminated early due to insufficient evidence of single-agent activity, the durable CR and 2 minor responses suggest that there may be a subset of EG patients who could benefit from this drug. Keywords Heat shock protein . Esophagogastric cancer . Phase II . Clinical trial . HER2
Introduction Esophagogastric cancer is the 2nd leading cause of cancer-related death worldwide [1]. Surgical resection remains the most Lipika Goyal and Surendra Pal Chaudhary contributed equally to this work. * Surendra Pal Chaudhary [email protected] 1
Harvard Medical School, Boston, MA, USA
2
Massachusetts General Hospital Cancer Center, 55 Fruit Street, 223 Bartlett Hall, Boston 02114, MA, USA
3
Dana Farber Cancer Institute, Boston, MA, USA
4
Virginia Cancer Specialist, Fairfax, VA, USA
effective and mainstay curative treatment [2]. Only a limited number of patients are amenable for surgical resection, and most patients present with locally advanced or
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