A real-world comparison of treatment strategies for metastatic pancreatic cancer: 4-month FOLFIRINOX followed by maintenance therapy versus 6-month FOLFIRINOX followed by observation
Authors
Kjær, Martin Olesen ; Kjærgaard, Joakim Kitete
Term
5. Term (Master thesis)
Education
Publication year
2025
Pages
17
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis. The FOLFIRINOX chemotherapy regimen can extend survival but often causes substantial side effects. The PANOPTIMOX‑PRODIGE 35 trial (2021) showed that after about 4 months of FOLFIRINOX, switching to a lighter maintenance therapy with 5‑FU (fluorouracil) preserved quality of life and overall survival compared with 6 months of full chemotherapy followed by a treatment pause. Objective: To compare these two strategies in routine practice, focusing on overall survival (OS, time from start of treatment to death) and progression‑free survival (PFS, time until the disease worsens or the patient dies), and to describe patient treatment pathways. Methods: In a retrospective cohort, 118 patients treated with FOLFIRINOX between October 2020 and October 2025 were identified; 90 were included in statistical analyses. Patients were grouped into a maintenance group (MG, n=24) receiving 5‑FU maintenance, a pause group (PG, n=15) taking a treatment break, and a deviation group (DG, n=51) who followed other courses. The primary endpoint was OS; PFS was secondary. Treatment courses were illustrated with a Sankey plot (flow diagram). Results: Mean age was 66 years; 56% were male and 44% female. Hospitalization during first‑line treatment occurred in 29% of MG, 47% of PG, and 71% of DG (p=0.003). Median OS for the whole cohort was 12.0 months, and median PFS was 8 months. By group, median OS was 22.6 months in MG and 14.2 months in PG (p=0.222). Among resected patients, median OS was 22.5 months versus 11.5 months in non‑resected patients (p=0.033). Median PFS was 11.0 months in MG and 9.1 months in PG (p=0.999). In Cox regression using DG as the reference, the hazard ratio (HR, relative risk of death) was 0.259 for MG (p<0.001) and 0.697 for PG (p=0.260); HRs below 1 indicate lower relative risk of death. Conclusion: In this real‑world cohort, findings align with PANOPTIMOX‑PRODIGE 35, suggesting that 5‑FU maintenance after initial FOLFIRINOX may achieve survival comparable to pausing treatment. The maintenance group also had fewer hospitalizations. Interpretation is limited by the inability to perform an intention‑to‑treat analysis, potential confounding due to treatment selection, and low protocol adherence, which led to small MG/PG samples while DG comprised over half the cohort. Results should be interpreted with caution.
Baggrund: Pankreatisk duktalt adenokarcinom (PDAC) har en meget dårlig prognose. Kemoregimet FOLFIRINOX kan forbedre overlevelsen, men giver ofte betydelige bivirkninger. Studiet PANOPTIMOX‑PRODIGE 35 (2021) viste, at man efter cirka 4 måneders FOLFIRINOX kan skifte til en mildere vedligeholdelsesbehandling med 5‑FU (fluorouracil) og bevare både livskvalitet og samlet overlevelse sammenlignet med 6 måneders fuld kemoterapi efterfulgt af behandlingspause. Formål: At sammenligne disse to strategier i klinisk praksis med fokus på samlet overlevelse (OS, tid fra behandlingsstart til død) og progressionsfri overlevelse (PFS, tid til sygdomsforværring eller død) samt at beskrive patienternes behandlingsforløb. Metoder: I et retrospektivt kohortestudie blev 118 patienter, som modtog FOLFIRINOX mellem oktober 2020 og oktober 2025, identificeret; 90 indgik i de statistiske analyser. Patienterne blev grupperet i en vedligeholdelsesgruppe (MG, n=24) med 5‑FU‑vedligehold, en pausegruppe (PG, n=15) med behandlingspause, og en afvigelsesgruppe (DG, n=51) som afveg fra disse strategier. Primært endepunkt var OS; sekundært PFS. Behandlingsforløb blev visualiseret i et Sankey‑diagram (flowdiagram). Resultater: Den gennemsnitlige alder var 66 år; 56% var mænd og 44% kvinder. Andelen med indlæggelser under 1. linjes behandling var 29% i MG, 47% i PG og 71% i DG (p=0,003). Den samlede median‑OS i kohorten var 12,0 måneder, og median‑PFS var 8 måneder. På gruppeniveau var median‑OS 22,6 måneder i MG mod 14,2 måneder i PG (p=0,222). Hos opererede patienter (resecerede) var median‑OS 22,5 måneder mod 11,5 måneder hos ikke‑opererede (p=0,033). Median‑PFS var 11,0 måneder i MG og 9,1 måneder i PG (p=0,999). I en Cox‑regression med DG som reference var hazard ratio (HR, relativ dødsrisiko) 0,259 for MG (p<0,001) og 0,697 for PG (p=0,260); HR under 1 indikerer lavere relativ risiko for død. Konklusion: I denne virkelighedsnære kohorte støtter resultaterne konklusionen fra PANOPTIMOX‑PRODIGE 35 om, at 5‑FU‑vedligehold efter indledende FOLFIRINOX kan give en overlevelse på linje med behandlingspause. Samtidig sås færre indlæggelser i vedligeholdelsesgruppen. Fortolkningen begrænses af, at intention‑to‑treat‑analyse ikke var mulig, mulig confounding ved valg af strategi, samt lav adherence med små gruppestørrelser i MG og PG og over halvdelen i DG. Resultaterne bør derfor tolkes med forsigtighed.
[This apstract has been rewritten with the help of AI based on the project's original abstract]