The value of FOLFIRINOX in advanced pancreatic cancer: balancing efficacy, toxicity, and quality of life.

[PURPOSE] Balancing therapeutic benefit and treatment burden remains a major challenge in administering FOLFIRINOX for advanced pancreatic ductal adenocarcinoma (PDAC). More than 60% of patients experience grade ≥ 3 adverse events (AEs), and only about 30% achieve a tumour response. This study examines the value of FOLFIRINOX chemotherapy by contextualising treatment efficacy, toxicity, and durability of response within ethical, financial, and person-centred frameworks. The aim is to support shared decision-making and optimise clinical outcomes and quality of life.

[METHODS] Patients with advanced PDAC receiving palliative FOLFIRINOX were included. Radiologic response was assessed using RECIST 1.1 at sequential time points during and after therapy. Patients were classified as having either progressive disease or disease control, the latter encompassing complete response, partial response, and stable disease.

[RESULTS] Amongst 84 advanced PDAC patients, 14 (17%) discontinued FOLFIRINOX before completing four cycles due to grade ≥ 3 AEs. Another four patients (5%) terminated FOLFIRINOX treatment after four cycles despite exhibiting disease control. Overall, 36 (43%) patients had at least one FOLFIRINOX-related grade ≥ 3 AE. Amongst the 66 patients who completed ≥ 4 cycles, 52 (79%) achieved disease control at FOLFIRINOX completion. However, disease control declined rapidly after therapy, falling to 41% at 6 months, 21% at 1 year, and 11% at 2 years. LAPC patients achieved disease control more frequently than patients with metastatic disease. Nevertheless, both groups experienced steep declines in disease control over time, from 85% and 69% at treatment completion to 32% and 4% at 1 year in LAPC and metastatic PDAC, respectively. Overall, 36 patients (55%) received subsequent systemic or locoregional therapies, most commonly gemcitabine/nab-paclitaxel (6%), SBRT (17%), or immunotherapy combined with SBRT (11%).

[CONCLUSION] Whilst FOLFIRINOX achieves high initial disease control in advanced PDAC, its benefit is limited by substantial toxicity and poor durability. Only a minority of patients maintain disease control beyond 6 months, which is strongly associated with improved survival. These findings suggest a need to redefine 'valuable FOLFIRINOX chemotherapy' to encompass not only initial response but also sustained disease control, toxicity management, and shared decision-making to optimise the benefit of FOLFIRINOX for patients.