FOLFIRINOX for pancreatic cancer: a real-world registry analysis

I read with keen interest the recent article by Engelke et al., titled “FOLFIRINOX versus gemcitabine (plus paclitaxel) for pancreatic cancer—an analysis based on data from the Clinical Cancer Registry of Lower Saxony” published in Annals of Pancreatic Cancer (1). This retrospective registry-based study significantly expands upon existing clinical trial evidence by leveraging real-world data to evaluate the comparative effectiveness of chemotherapy regimens in pancreatic cancer.

The authors’ observation that FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) confers a survival advantage over both gemcitabine monotherapy and the gemcitabine plus paclitaxel combination represents an important validation of randomized clinical trial outcomes within a broader, unselected patient population. Their findings align well with current National Comprehensive Cancer Network (NCCN) guideline recommendations (2) and underscore the utility of registry data to capture real-world treatment patterns and outcomes more comprehensively than clinical trials alone (3).

Nonetheless, some methodological limitations warrant further discussion. As an observational retrospective study, unmeasured confounding factors may have influenced the survival differences observed. Notably, the absence of complete data on Eastern Cooperative Oncology Group (ECOG) performance status and comorbidities restricts the ability to ascertain patient eligibility for specific guideline-endorsed regimens, thereby limiting insights into the impact of guideline adherence on outcomes (1). Moreover, the heterogeneous ‘other chemotherapy regimens’ group, which paradoxically exhibited a lower adjusted risk of death than FOLFIRINOX, is likely subject to immortal time bias, thus constraining its interpretability. Additionally, grouping gemcitabine monotherapy and gemcitabine plus paclitaxel under a single umbrella in certain analyses may mask important distinctions in efficacy and toxicity between these regimens (4).

Importantly, the study does not address treatment-related toxicities or quality-of-life outcomes, which are critical considerations given the known high toxicity profile of FOLFIRINOX (4). Real-world data on dose modifications, discontinuation rates, and patient tolerability would provide valuable context to balance survival benefits against adverse effects outside controlled trial settings. Lastly, as the dataset reflects a regional registry limited to Lower Saxony, the generalizability of these findings to other healthcare systems with differing treatment protocols and patient demographics remains uncertain.

In conclusion, Engelke et al. offer compelling real-world evidence supporting the superior survival benefit of FOLFIRINOX in pancreatic cancer (1), reinforcing guideline recommendations (2), and highlighting the strengths of registry data in supplementing clinical trials (3). Moving forward, enhancing registry data quality by incorporating comprehensive clinical parameters such as performance status and comorbidities, alongside patient-reported outcomes including toxicity and quality of life, will be essential to fully elucidate treatment effectiveness and tolerability in routine clinical practice.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was a standard submission to the journal. The article did not undergo external peer review.

Funding: None.

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (https://apc.amegroups.com/article/view/10.21037/apc-25-18/coif). The author has no conflicts of interest to declare.

Ethical Statement: The author is accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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References

1. Engelke J, Klora M, Zeidler J, et al. FOLFIRINOX versus gemcitabine (plus paclitaxel) for pancreatic cancer—an analysis based on data from the Clinical Cancer Registry of Lower Saxony. Ann Pancreat Cancer 2025;8:8.
2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Pancreatic Adenocarcinoma. Version 3.2025. Available online: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455
3. Blomstrand H, Batra A, Cheung WY, et al. Real-world evidence on first- and second-line palliative chemotherapy in advanced pancreatic cancer. World J Clin Oncol 2021;12:787-99. [Crossref] [PubMed]
4. Chan KKW, Guo H, Cheng S, et al. Real-world outcomes of FOLFIRINOX vs gemcitabine and nab-paclitaxel in advanced pancreatic cancer: A population-based propensity score-weighted analysis. Cancer Med 2020;9:160-9. [Crossref] [PubMed]