In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 3_suppl ( 2015-01-20), p. 177-177
Abstract:
177 Background: Adenocarcinomas of the distal esophagus, gastroesophageal junction and stomach (GEC) remain challenging cancers to treat. Unfortunately, 80-90% of newly diagnosed patients (pts) present with advanced disease where the overall median survival (mOS) is less than 1 year. Discouragingly, various common first-line metastatic regimens have similar overall response rates (ORR) (30-40%; and 47% for HER2+ with trastuzumab). Given results within other GI tumors, FOLFIRINOX was administered to pts with newly diagnosed advanced GEC. Methods: A pooled analysis from two independent ongoing clinical trials was conducted from: 1) the University of Chicago UC (NCT01643499) where pts received modified ‘mFOLFIRINOX’ with irinotecan dosing based on UGT1A1*28 genotyping; and 2) Washington University (WU) (NCT01928290) where pts received standard ‘sFOLFIRINOX’ as previously described, and HER2+ pts also received trastuzumab (sFOLFIRINOX-T). Both studies administered therapy every 14 days. Trastuzumab was administered as 6 mg/kg loading dose then 4 mg/kg every 14 days. mFOLFIRINOX used UGT1A1 genotype *1/*1, *1/*28, and *28/*28 to assign initial irinotecan doses of 180, 135, and 90 mg/m 2 , respectively. The mFOLFIRINOX 5-FU dose was 2400 mg/m 2 over 46 hours (no bolus) with leucovorin 400 mg/m 2 , and oxaliplatin 85 mg/m 2 . Outcomes included ORR, tolerability/safety, mPFS, and mOS for both trials. Results: In the pooled analysis, 18 pts with GEC were enrolled to date (11 at WU and 7 at UC), and 16 evaluable for response. ORR was 62.5% (10/16), (HER2- 58% (7/12), HER2+ 75% (3/4)). One HER2+ pt experienced a CR. mPFS was 8 months (range 1.5-18 months), however 10/16 pts have not progressed on first-line therapy to date. There were no unexpected toxicities for any of the regimens. Conclusions: ORR and PFS with first-line FOLFIRINOX were encouraging for metastatic GEC. sFOLFIRINOX was well tolerated in these patients, and sFOLFIRINOX-T was safely administered.mFOLFIRINOX consisting of genotype-directed irinotecan dose reductions and no 5FU bolus may limit toxicity yet retain similar benefit to sFOLFIRINOX. Continued investigation of this regimen is warranted given these encouraging preliminary results. Clinical trial information: 01928290.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2015.33.3_suppl.177
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2015
detail.hit.zdb_id:
2005181-5
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