Adjuvant Modified FOLFIRINOX for Resected Pancreatic Adenocarcinoma (PDAC): Clinical Insights and Genomic Features from a Large Contemporary Cohort.


Journal

Journal of the National Cancer Institute
ISSN: 1460-2105
Titre abrégé: J Natl Cancer Inst
Pays: United States
ID NLM: 7503089

Informations de publication

Date de publication:
26 Oct 2024
Historique:
received: 24 07 2024
revised: 26 09 2024
accepted: 17 10 2024
medline: 26 10 2024
pubmed: 26 10 2024
entrez: 26 10 2024
Statut: aheadofprint

Résumé

Adjuvant mFOLFIRINOX (mFFX) is standard of care for fit individuals with resected pancreatic ductal adenocarcinoma (PDAC). There are limited data on adjuvant mFFX outcomes outside clinical trials. Institutional databases queried to identify patients with resected PDAC who received ≥1 dose adjuvant mFFX. Primary endpoints: recurrence free survival (RFS), overall survival (OS). Secondary endpoints: clinical factors, genomic features associated with outcomes. RFS and OS were estimated with Kaplan-Meier. Cox proportional hazards regression model was used to associate clinico-genomic features correlated with survival outcomes. N = 147 identified between 01/2015-01/2023. Median age: 67 years; N = 57 (39%) >70 years. Unfavorable prognostic features: N = 52 (36%) N2 nodal status, N = 115 (78%) lymphovascular invasion), and N = 133 (90%) perineural invasion. Median time from surgery to start mFFX: 1.78 months (m) (IQR 1.45, 2.12). N = 124 (84%) completed 12 doses; N = 98 (67%) stopped oxaliplatin early for neuropathy (median 10 doses; range 4-12). Further dosing characteristics are summarized in Supplementary Table 3. With median follow up of 35.1 m, median RFS (mRFS) 26 m (95% CI 19, 39) and median OS (mOS) not reached. For >70 cohort, mRFS 23 m (95% CI 14, NR) and mOS 51 m (95% CI 37, NR). mFFX started <8 weeks from resection associated with improved RFS (HR 0.62; 95% CI 0.41, 0.96; p = .033) and OS (HR 0.53; 95% CI 0.3, 0.94; p = .030). KRAS mutation and whole genome doubling trended to shorter RFS and OS. Homologous recombination deficiency status did not confer improved survival outcomes. Adjuvant mFFX is effective and tolerable in resected PDAC in a non-trial setting, including for patients >70 years.

Sections du résumé

BACKGROUND BACKGROUND
Adjuvant mFOLFIRINOX (mFFX) is standard of care for fit individuals with resected pancreatic ductal adenocarcinoma (PDAC). There are limited data on adjuvant mFFX outcomes outside clinical trials.
METHODS METHODS
Institutional databases queried to identify patients with resected PDAC who received ≥1 dose adjuvant mFFX. Primary endpoints: recurrence free survival (RFS), overall survival (OS). Secondary endpoints: clinical factors, genomic features associated with outcomes. RFS and OS were estimated with Kaplan-Meier. Cox proportional hazards regression model was used to associate clinico-genomic features correlated with survival outcomes.
RESULTS RESULTS
N = 147 identified between 01/2015-01/2023. Median age: 67 years; N = 57 (39%) >70 years. Unfavorable prognostic features: N = 52 (36%) N2 nodal status, N = 115 (78%) lymphovascular invasion), and N = 133 (90%) perineural invasion. Median time from surgery to start mFFX: 1.78 months (m) (IQR 1.45, 2.12). N = 124 (84%) completed 12 doses; N = 98 (67%) stopped oxaliplatin early for neuropathy (median 10 doses; range 4-12). Further dosing characteristics are summarized in Supplementary Table 3. With median follow up of 35.1 m, median RFS (mRFS) 26 m (95% CI 19, 39) and median OS (mOS) not reached. For >70 cohort, mRFS 23 m (95% CI 14, NR) and mOS 51 m (95% CI 37, NR). mFFX started <8 weeks from resection associated with improved RFS (HR 0.62; 95% CI 0.41, 0.96; p = .033) and OS (HR 0.53; 95% CI 0.3, 0.94; p = .030). KRAS mutation and whole genome doubling trended to shorter RFS and OS. Homologous recombination deficiency status did not confer improved survival outcomes.
CONCLUSIONS CONCLUSIONS
Adjuvant mFFX is effective and tolerable in resected PDAC in a non-trial setting, including for patients >70 years.

Identifiants

pubmed: 39460946
pii: 7845262
doi: 10.1093/jnci/djae269
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Auteurs

Fergus Keane (F)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.
David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Catherine O'Connor (C)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.
David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Harvard Medical School, Boston, MA, USA.

Drew Moss (D)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.
David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Icahn School of Medicine at Mount, Sinai Morningside-West, New York, NY, USA.

Joanne F Chou (JF)

Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.

Maria A Perry (MA)

Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.

Fionnuala Crowley (F)

Department of Hematology Oncology, Icahn School of Medicine at Mount Sinai.
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai.
Brookdale Department Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai.

Parima Saxena (P)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.

Amelia Chan (A)

Pharmacy Department, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.

Joshua D Schoenfeld (JD)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.
David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Anupriya Singhal (A)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.
David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Wungki Park (W)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.
David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Medicine, Weill Cornell Medical College, New York, NY, USA.

Darren Cowzer (D)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.

Emily Harrold (E)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.

Anna M Varghese (AM)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.
David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Medicine, Weill Cornell Medical College, New York, NY, USA.

Imane El Dika (I)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.
David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Medicine, Weill Cornell Medical College, New York, NY, USA.

Christopher Crane (C)

David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Trinity College, Dublin, Ireland.

James J Harding (JJ)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.
David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Medicine, Weill Cornell Medical College, New York, NY, USA.

Ghassan K Abou-Alfa (GK)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.
David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
Trinity College, Dublin, Ireland.

T Peter Kingham (TP)

David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.

Alice C Wei (AC)

David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.

Kenneth H Yu (KH)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.
David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Medicine, Weill Cornell Medical College, New York, NY, USA.

Michael I D'Angelica (MI)

David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.

Vinod P Balachandran (VP)

David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.

Jeffrey Drebin (J)

David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.

William R Jarnagin (WR)

David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.

Chaitanya Bandlamudi (C)

Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.

David Kelsen (D)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.
David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Medicine, Weill Cornell Medical College, New York, NY, USA.

Marinela Capanu (M)

Harvard Medical School, Boston, MA, USA.

Kevin C Soares (KC)

David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Trinity College, Dublin, Ireland.

Fiyinfolu Balogun (F)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.
David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Medicine, Weill Cornell Medical College, New York, NY, USA.

Eileen M O'Reilly (EM)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, 10065, NY, USA.
David M. Rubenstein Center for Pancreas Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai.
Trinity College, Dublin, Ireland.

Classifications MeSH