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Clinical Trial
. 2020 Aug 1;6(8):1231-1240.
doi: 10.1001/jamaoncol.2020.2020.

FOLFIRINOX for the Treatment of Advanced Gastroesophageal Cancers: A Phase 2 Nonrandomized Clinical Trial

Haeseong Park  1 , Ramon U Jin  1 , Andrea Wang-Gillam  1 , Rama Suresh  1 , Caron Rigden  1 , Manik Amin  1 , Benjamin R Tan  1 , Katrina S Pedersen  1 , Kian-Huat Lim  1 , Nikolaos A Trikalinos  1 , Abhilasha Acharya  1 , Megan L Copsey  1 , Katherine A Navo  1 , Ashley E Morton  1 , Feng Gao  2 , A Craig Lockhart  3
Affiliations
Clinical Trial

FOLFIRINOX for the Treatment of Advanced Gastroesophageal Cancers: A Phase 2 Nonrandomized Clinical Trial

Haeseong Park et al. JAMA Oncol. .

Abstract

Importance: Standard 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.

Objective: To evaluate the clinical activity and safety of FOLFIRINOX as first-line treatment for patients with advanced gastroesophageal adenocarcinoma.

Design, setting, and participants: This 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.

Interventions: Starting 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 measures: The 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.

Results: From 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 relevance: The 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 registration: ClinicalTrials.gov Identifier: NCT01928290.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Park reported that her institution received grants from the following commercial entities and that she served as the site principal investigator for studies funded by these entities: Ambrx, Amgen, Array BioPharma, Bayer, BeiGene, BJ Bioscience, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly and Company, EMD Serono, Five Prime Therapeutics, Genentech, Gilead Sciences, GlaxoSmithKline, Hoffmann-La Roche, ImmuneOncia Therapeutics, Immunomedics, Incyte, MacroGenics, MedImmune, Medivation, Merck & Co, Millennium Pharmaceuticals, Mirati Therapeutics, Novartis Pharmaceuticals, Oncologie, Pfizer, PsiOxus Therapeutics, Puma Biotechnology, Regeneron Pharmaceuticals, Synermore Biologics, Taiho Pharmaceutical, TopAlliance Biosciences, Turning Point Therapeutics, Vedanta Biosciences, Vertex Pharmaceuticals, and Xencor Inc. Dr Morton reported having a previous relationship with Guardant Health/Guardant360 as part of the nursing speakers bureau. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Flowchart
Figure 2.
Figure 2.. Treatment Response Among 67 Patients With ERBB2-Negative and ERBB2-Positive Advanced Gastroesophageal Cancer Treated With FOLFIRINOX
A, Best percentage change in target lesions from baseline in patients with ERBB2-negative disease. Each bar represents a patient. Dotted lines indicate changes in target lesion size of −30% and +20%. B, Time to and duration of response in patients with ERBB2-negative disease. C, Best percentage change in target lesions from baseline in patients with ERBB2-positive disease. D, Time to and duration of response in patients with ERBB2-positive disease. CR indicates complete response; FOLFIRINOX, leucovorin, fluorouracil, irinotecan, and oxaliplatin; ORR, objective response rate; PD, progressive disease; PR, partial response; SD, stable disease.
Figure 3.
Figure 3.. Progression-Free Survival (PFS) and Overall Survival (OS) of Patients With Advanced Gastroesophageal Cancer Treated With First-line FOLFIRINOX
A, PFS in patients with ERBB2-negative disease. B, OS in patients with ERBB2-negative disease. C, PFS in patients with ERBB2-positive disease. D, OS in patients with ERBB2-positive disease. FOLFIRINOX indicates a combination of leucovorin, fluorouracil, irinotecan, and oxaliplatin.
See this image and copyright information in PMC

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