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

Clin Cancer Res. 2021 Dec 1;27(23):6343-6353. doi: 10.1158/1078-0432.CCR-21-0331. Epub 2021 Jul 30.

Abstract

Purpose: We performed a NCI-sponsored, prospective study of neoadjuvant FOLFIRINOX followed by chemoradiation with carboplatin/paclitaxel followed by surgery in patients with locally advanced gastric or gastroesophageal cancer.

Patients and methods: The primary objective was to determine completion rate of neoadjuvant FOLFIRINOX × 8 followed by chemoradiation. Secondary endpoints were toxicity and pathologic complete response (pCR) rate. Exploratory analysis was performed of circulating tumor DNA (ctDNA) to treatment response.

Results: From October 2017 to June 2018, 25 patients were enrolled. All patients started FOLFIRINOX, 92% completed all eight planned cycles, and 88% completed chemoradiation. Twenty (80%) patients underwent surgical resection, and 7 had a pCR (35% in resected cohort, 28% intention to treat). Tumor-specific mutations were identified in 21 (84%) patients, of whom 4 and 17 patients had undetectable and detectable ctDNA at baseline, respectively. Presence of detectable post-chemoradiation ctDNA (P = 0.004) and/or postoperative ctDNA (P = 0.045) were associated with disease recurrence.

Conclusions: Here we show neoadjuvant FOLFIRINOX followed by chemoradiation for locally advanced gastroesophageal cancer is feasible and yields a high rate of pCR. ctDNA appears to be a promising predictor of postoperative recurrence.See related commentary by Catenacci, p. 6281.

Trial registration: ClinicalTrials.gov NCT03279237.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma* / drug therapy
  • Adenocarcinoma* / therapy
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Fluorouracil
  • Humans
  • Irinotecan
  • Leucovorin
  • Neoadjuvant Therapy / methods
  • Neoplasm Recurrence, Local
  • Oxaliplatin
  • Pancreatic Neoplasms* / pathology
  • Pilot Projects
  • Prospective Studies
  • Treatment Outcome

Substances

  • folfirinox
  • Oxaliplatin
  • Irinotecan
  • Leucovorin
  • Fluorouracil

Associated data

  • ClinicalTrials.gov/NCT03279237