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

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.

• Authors: Jennifer Y Wo, Jeffrey W Clark, Christine E Eyler, Mari Mino-Kenudson, Samuel J Klempner, Jill N Allen, Florence K Keane, Aparna R Parikh, Eric Roeland, Lorraine C Drapek, David P Ryan, Ryan B Corcoran, Emily Van Seventer, Isobel J Fetter, Heather A Shahzade, Melin J Khandekar, Michael Lanuti, Christopher R Morse, Rebecca S Heist, Christine A Ulysse, Benjamin Christopher, Christian Baglini, Beow Y Yeap, John T Mullen, Theodore S Hong
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 27 Issue 23 Pg. 6343-6353 (12 01 2021) ISSN: 1557-3265 [Electronic] United States
• PMID: 34330715 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: ©2021 American Association for Cancer Research.

Chemical References

• folfirinox
• Oxaliplatin
• Irinotecan
• Leucovorin
• Fluorouracil

Topics

• Adenocarcinoma (drug therapy, 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