FOLFIRINOX as first-line therapy in patients with metastatic gastroesophageal cancers (GEC).

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/m2, respectively. The mFOLFIRINOX 5-FU dose was 2400 mg/m2 over 46 hours (no bolus) with leucovorin 400 mg/m2, and oxaliplatin 85 mg/m2. 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.

Pilot trial of CRLX101 in patients with advanced, chemotherapy-refractory gastroesophageal cancer

“…Based on these results, a phase I study is ongoing combining weekly CRLX101 in combination with fluorouracil/leucovorin/oxaliplatin combination chemotherapy (modified FOLFOX6) in advanced solid tumors including gastrointestinal cancers (Clinicaltrials.gov NCT02648711). Phase II studies of the triplet combination of irinotecan/fluorouracil/oxaliplatin (FOLFOXIRI or FOLFIRINOX) have demonstrated promising ORRs of >60% as first-line therapy for advanced gastric cancer (19)(20)(21). As such, the combination of CRLX101 with mFOLFOX6 could be promising in gastroesophageal cancer patients.…”

A rare case of esophageal metastasis from pancreatic ductal adenocarcinoma: a case report and literature review

“…Since then, FOLFIRINOX has been studied in other settings of PDAC as well as other gastrointestinal cancers, with promising response rates in patients who are able to tolerate the regimen. [ 32 - 35 ]…”

Results and Molecular Correlates from a Pilot Study of Neoadjuvant Induction FOLFIRINOX Followed by Chemoradiation and Surgery for Gastroesophageal Adenocarcinomas

“…Outside of GEA, FOLFIRINOX has emerged as a standard of care for pancreatic cancer in both the resectable and metastatic setting 13,14 . Additionally, there is a growing body of literature evaluating the e cacy of this regimen in gastroesophageal and gastric cancers [15][16][17] . A pooled analysis of two ongoing Phase II trials of FOLFIRINOX in the rst line metastatic setting for GE junction cancers demonstrated an overall response rate (ORR) of 62.5% 15 .…”

“…Additionally, there is a growing body of literature evaluating the e cacy of this regimen in gastroesophageal and gastric cancers [15][16][17] . A pooled analysis of two ongoing Phase II trials of FOLFIRINOX in the rst line metastatic setting for GE junction cancers demonstrated an overall response rate (ORR) of 62.5% 15 . In a recently published phase II trial of advanced GEA, among ERBB2-negative patients treated with FOLFIRINOX alone, the ORR was 61%, with a median overall survival of 15.5 months.…”