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Systemic therapy for advanced gastroesophageal cancers: progress and pitfalls.

ABSTRACT: Advanced gastroesophageal cancer in which surgical resection is no longer appropriate is an aggressive malignancy with poor prognosis. This review provides an overview of the key trials that have led to the current standard of care, both highlighting progress with systemic cytotoxic and biological therapies, but also calling attention to pitfalls to assist practitioners in optimizing currently available treatments for their patients. This review surveys recent and ongoing trials and biomarker studies regarding the use of anti-HER2 agents, with increased recognition of molecular intratumoral heterogeneity confounding such targeted therapy strategies. We conclude with an overview of recent major trials incorporating immune checkpoint inhibitors among patients with metastatic and locally advanced gastroesophageal cancer and providing a framework for the discriminate application of these new therapies.

SUBMITTER: Epistola RJ

PROVIDER: S-EPMC7530312 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Systemic therapy for advanced gastroesophageal cancers: progress and pitfalls.

Epistola Raisa J RJ Chao Joseph J

Translational gastroenterology and hepatology 20201005

Advanced gastroesophageal cancer in which surgical resection is no longer appropriate is an aggressive malignancy with poor prognosis. This review provides an overview of the key trials that have led to the current standard of care, both highlighting progress with systemic cytotoxic and biological therapies, but also calling attention to pitfalls to assist practitioners in optimizing currently available treatments for their patients. This review surveys recent and ongoing trials and biomarker st ...[more]

PMID: 33073048

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Project description:ImportanceStandard first-line regimens for patients with metastatic gastroesophageal adenocarcinomas have an approximate 40% objective response rate (ORR). The combination of leucovorin, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) has been efficacious as first-line therapy for other gastrointestinal cancers, such as pancreatic and colon cancers.ObjectiveTo evaluate the clinical activity and safety of FOLFIRINOX as first-line treatment for patients with advanced gastroesophageal adenocarcinoma.Design, setting, and participantsThis is an open-label, single-arm phase 2 study of first-line FOLFIRINOX in patients with advanced gastroesophageal adenocarcinoma. Estimated sample size included 41 patients with ERBB2-negative disease with 90% power to detect an ORR of 60% or greater with α of .10. No enrollment goal was planned for ERBB2-positive patients, but they were allowed to receive trastuzumab in combination with FOLFIRINOX.InterventionsStarting doses were fluorouracil, 400 mg/m2 bolus, followed by 2400 mg/m2 over 46 hours; leucovorin, 400 mg/m2; irinotecan, 180 mg/m2; and oxaliplatin, 85 mg/m2. Trastuzumab was administered as a 6 mg/kg loading dose, followed by 4 mg/kg every 14 days in patients with ERBB2-positive disease.Main outcomes and measuresThe primary end point was ORR by the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included safety profile, progression-free survival (PFS), overall survival (OS), and duration of response.ResultsFrom November 2013 to May 2018, 67 patients were enrolled (median [range] age, 59.0 [34-78] years; including 56 [84%] men), and 26 of 67 (39%) had ERBB2-positive disease. Median follow-up was 17.4 months. The ORR was 61%(95% CI, 44.5%-75.8%) (25 of 41) in the ERBB2-negative group and 85% (95% CI, 65.1%-95.6%) (22 of 26) in the ERBB2-positive group, including 1 patient with complete response. For ERBB2-negative patients, median PFS was 8.4 months and median OS was 15.5 months; for ERBB2-positive patients, median PFS was 13.8 months and median OS was 19.6 months. Fifty-six patients (84%) had dose modifications or treatment delays. The most common toxic effects were neutropenia (91%, n = 61), diarrhea (63%, n = 42), peripheral sensory neuropathy (61%, n = 41), and nausea (48%, n = 32), with no unexpected toxic effects.Conclusions and relevanceThe FOLFIRINOX regimen with or without trastuzumab was associated with improved ORR and PFS in patients with advanced gastroesophageal adenocarcinoma in the first-line setting. This regimen may be a reasonable therapeutic option for patients with preserved performance status.Trial registrationClinicalTrials.gov Identifier: NCT01928290.

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Systemic therapy for advanced gastroesophageal cancers: progress and pitfalls.

Publications

Systemic therapy for advanced gastroesophageal cancers: progress and pitfalls.

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