A phase 2 clinical trial of the heat shock protein 90 (HSP 90) inhibitor ganetespib in patients with refractory advanced esophagogastric cancer.

Autor: Goyal L; Harvard Medical School, Boston, MA, USA.; Massachusetts General Hospital Cancer Center, 55 Fruit Street, 223 Bartlett Hall, Boston, 02114, MA, USA., Chaudhary SP; Harvard Medical School, Boston, MA, USA. Schaudhary1@mgh.harvard.edu.; Massachusetts General Hospital Cancer Center, 55 Fruit Street, 223 Bartlett Hall, Boston, 02114, MA, USA. Schaudhary1@mgh.harvard.edu., Kwak EL; Harvard Medical School, Boston, MA, USA.; Massachusetts General Hospital Cancer Center, 55 Fruit Street, 223 Bartlett Hall, Boston, 02114, MA, USA., Abrams TA; Harvard Medical School, Boston, MA, USA.; Dana Farber Cancer Institute, Boston, MA, USA., Carpenter AN; Massachusetts General Hospital Cancer Center, 55 Fruit Street, 223 Bartlett Hall, Boston, 02114, MA, USA., Wolpin BM; Harvard Medical School, Boston, MA, USA.; Dana Farber Cancer Institute, Boston, MA, USA., Wadlow RC; Virginia Cancer Specialist, Fairfax, VA, USA., Allen JN; Harvard Medical School, Boston, MA, USA.; Massachusetts General Hospital Cancer Center, 55 Fruit Street, 223 Bartlett Hall, Boston, 02114, MA, USA., Heist R; Harvard Medical School, Boston, MA, USA.; Massachusetts General Hospital Cancer Center, 55 Fruit Street, 223 Bartlett Hall, Boston, 02114, MA, USA., McCleary NJ; Harvard Medical School, Boston, MA, USA.; Dana Farber Cancer Institute, Boston, MA, USA., Chan JA; Harvard Medical School, Boston, MA, USA.; Dana Farber Cancer Institute, Boston, MA, USA., Goessling W; Harvard Medical School, Boston, MA, USA.; Dana Farber Cancer Institute, Boston, MA, USA., Schrag D; Harvard Medical School, Boston, MA, USA.; Dana Farber Cancer Institute, Boston, MA, USA., Ng K; Harvard Medical School, Boston, MA, USA.; Dana Farber Cancer Institute, Boston, MA, USA., Enzinger PC; Harvard Medical School, Boston, MA, USA.; Dana Farber Cancer Institute, Boston, MA, USA., Ryan DP; Harvard Medical School, Boston, MA, USA.; Massachusetts General Hospital Cancer Center, 55 Fruit Street, 223 Bartlett Hall, Boston, 02114, MA, USA., Clark JW; Harvard Medical School, Boston, MA, USA.; Massachusetts General Hospital Cancer Center, 55 Fruit Street, 223 Bartlett Hall, Boston, 02114, MA, USA.
Jazyk: angličtina
Zdroj: Investigational new drugs [Invest New Drugs] 2020 Oct; Vol. 38 (5), pp. 1533-1539. Date of Electronic Publication: 2020 Jan 02.
DOI: 10.1007/s10637-019-00889-y
Abstrakt: 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.
Databáze: MEDLINE
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