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Phase II trial of everolimus in patients with refractory metastatic adenocarcinoma of the esophagus, gastroesophageal junction and stomach: possible role for predictive biomarkers.

Abstract：

PURPOSE:Our study was designed to evaluate the efficacy and safety of everolimus in patients with pre-treated metastatic gastric and esophagus cancers in a US-based population focusing on biomarker correlation. METHODS:Patients with advanced upper GI adenocarcinomas who progressed after 1-2 prior regimens received everolimus 10 mg PO daily. The primary endpoint was disease control rate (DCR). Secondary endpoints included progression-free survival (PFS), toxicity, overall survival (OS) and biomarker correlatives of the mTOR pathway. Target accrual was 50 patients based on one-sided type I error of 10 % and power of 90 %. RESULTS:Forty-five patients were evaluable, 21 gastric, 11 esophagus and 13 from the GEJ. The median age was 64 (range 38-73); all patients had an ECOG of 0 or 1; and 18 patients (40 %) had only 1 prior regimen. The most common grade 3-4 adverse events included fatigue (24 %) and thrombocytopenia (22 %). We observed 1 partial response with 39 % of evaluable patients having stable disease. Median OS was 3.4 months (95 % CI 2.7-5.6 months), and PFS was 1.8 months (95 % CI 1.7-2.2 months). There was a strong correlation between ≥2 + IHC staining for p-S6 in tumor samples with better PFS (p < 0.0001) and DCR (p = 0.0001). CONCLUSIONS:Our clinical outcomes were inferior to the Asian studies, which may be explained by disease heterogeneity. However, there was a similar strong correlation between clinical benefit and tumor high pS6. Testing this biomarker in patient samples from the randomized phase III Granite trial may lead to a positive predictive marker.

journal_name

Cancer Chemother Pharmacol

journal_title

Cancer chemotherapy and pharmacology

authors

Wainberg ZA,Soares HP,Patel R,DiCarlo B,Park DJ,Liem A,Wang HJ,Yonemoto L,Martinez D,Laux I,Brennan M,Hecht JR

doi

10.1007/s00280-015-2744-5

subject

Has Abstract

pub_date

2015-07-01 00:00:00

pages

61-7

issue

eissn

0344-5704

issn

1432-0843

journal_volume

pub_type

杂志文章,多中心研究

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Phase II trial of everolimus in patients with refractory metastatic adenocarcinoma of the esophagus, gastroesophageal junction and stomach: possible role for predictive biomarkers.