Synapse - Adjuvant modified FOLFIRINOX for resected pancreatic adenocarcinoma: Clinical insights and genomic features from a large contemporary cohort

Adjuvant modified FOLFIRINOX for resected pancreatic adenocarcinoma: Clinical insights and genomic features from a large contemporary cohort Journal Article

Authors:	Keane, F.; O’Connor, C.; Moss, D.; Chou, J. F.; Perry, M. A.; Crowley, F.; Saxena, P.; Chan, A.; Schoenfeld, J. D.; Singhal, A.; Park, W.; Cowzer, D.; Harrold, E.; Varghese, A. M.; El Dika, I.; Crane, C.; Harding, J. J.; Abou-Alfa, G. K.; Kingham, T. P.; Wei, A. C.; Yu, K. H.; D’Angelica, M. I.; Balachandran, V. P.; Drebin, J.; Jarnagin, W. R.; Bandlamudi, C.; Kelsen, D.; Capanu, M.; Soares, K. C.; Balogun, F.; O’Reilly, E. M.
Article Title:	Adjuvant modified FOLFIRINOX for resected pancreatic adenocarcinoma: Clinical insights and genomic features from a large contemporary cohort
Abstract:	Background: Adjuvant modified leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin (FOLFIRINOX) is standard of care for fit individuals with resected pancreatic ductal adenocarcinoma (PDAC). Data are limited on adjuvant modified FOLFIRINOX outcomes outside clinical trials. Methods: We queried institutional databases to identify patients with resected PDAC who received 1 or more doses of adjuvant modified FOLFIRINOX. Primary endpoints were recurrence-free survival (RFS) and overall survival. Secondary endpoints were clinical factors and genomic features associated with outcomes. We estimated RFS and overall survival by using the Kaplan-Meier method. A Cox proportional hazards regression model was used to associate clinicogenomic features with survival outcomes. Results: A search revealed 147 individuals with PDAC between January 2015 and January 2023. Median patient age was 67 years, with 57 (39%) patients older than 70 years. Unfavorable prognostic features included 52 (36%) patients with N2 nodal status, 115 (78%) patients with lymphovascular invasion, and 133 (90%) patients with perineural invasion. Median time from surgery to initiation of modified FOLFIRINOX was 1.78 months (IQR = 1.45-2.12). In total, 124 (84%) patients completed 12 doses; 98 (67%) patients stopped oxaliplatin early because of neuropathy (median = 10 doses, range = 4-12 doses). Further dosing characteristics are summarized in /3, with a median follow-up of 35.1 months, a median RFS of 26 months (95% confidence interval [CI] = 19 to 39), and a median overall survival not reached. For the cohort older than 70 years of age, the median RFS was 23 months (95% CI = 14 to not reached) and the median overall survival was 51 months (95% CI = 37 to not reached). Modified FOLFIRINOX started sooner than 8 weeks from resection was associated with improved RFS (hazard ratio = 0.62, 95% CI = 0.41 to 0.96; P = .033) and overall survival (hazard ratio = 0.53, 95% CI = 0.3 to 0.94; P = .030).KRAS variation and whole-genome doubling trended to shorter RFS and overall survival. Homologous recombination deficiency status did not confer improved survival outcomes. Conclusions: Adjuvant modified FOLFIRINOX was effective and tolerated in patients with resected PDAC in a nontrial setting, including for patients older than 70 years of age. © The Author(s) 2024. Published by Oxford University Press. All rights reserved.
Keywords:	aged; middle aged; retrospective studies; genetics; mortality; fluorouracil; chemotherapy, adjuvant; pancreatic neoplasms; antineoplastic agent; adenocarcinoma; antineoplastic combined chemotherapy protocols; carcinoma, pancreatic ductal; pathology; retrospective study; irinotecan; folinic acid; adjuvant chemotherapy; pancreas tumor; surgery; drug therapy; oxaliplatin; leucovorin; pancreatic ductal carcinoma; humans; prognosis; human; male; female; folfirinox
Journal Title:	JNCI: Journal of the National Cancer Institute
Volume:	117
Issue:	3
ISSN:	0027-8874
Publisher:	Oxford University Press
Date Published:	2025-03-01
Start Page:	496
End Page:	506
Language:	English
DOI:	10.1093/jnci/djae269
PUBMED:	39460946
PROVIDER:	scopus
PMCID:	PMC11884847
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-86000648902&doi=10.1093%2fjnci%2fdjae269&partnerID=40&md5=cecab88ad375908d40d6d9a6986e976d
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is Eileen M. O’Reilly -- Source: Scopus