Predictive criteria for overall survival and treatment duration of 2nd-line chemotherapy in patients with advanced pancreatic adenocarcinoma (AIO-PAK-0216)

Q: What was the main goal of the study in patients with advanced pancreatic adenocarcinoma?

To identify predictive factors, collected during routine clinical care, that can support informed decisions about 2nd-line chemotherapy outcomes.

Q: Does time-to-treatment-failure of 1st-line therapy (TTF1) predict 2nd-line outcomes?

No. TTF1 did not predict 2nd-line TTF2 or overall survival (OS).

Q: Which baseline factors were associated with TTF2 and OS?

Neutrophil count, CRP levels, and liver metastases were significantly associated with TTF2 and OS, while ECOG performance score was mainly associated with OS and to a lesser extent with TTF2.

Sep 29, 2026

Uploaded by Miles

Advanced pancreatic adenocarcinoma patients do not uniformly benefit from 2nd-line chemotherapy. A prospective multicenter study across 35 German sites assessed whether routine baseline and 1st-line time-to-treatment-failure (TTF1) predict outcomes after 2nd-line nanoliposomal irinotecan/5-fluorouracil/folinic acid. Among 151 patients, TTF1 was not predictive of 2nd-line TTF2 or overall survival (OS). Neutrophil count, CRP, and liver metastases correlated with TTF2 and OS, while CA 19-9 reduction ≥25% improved both endpoints.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages7

Reading Time18 min

AccessFree to download

Background

Methods and endpoints

Results

Conclusion

British Journal of Cancer [www.nature.com/bjc](www.nature.com/bjc) ARTICLE OPEN Clinical Studies Predictive criteria for overall survival and treatment duration of 2nd-line chemotherapy in patients with advanced pancreatic adenocarcinoma (AIO-PAK-0216) Manfred P. Lutz 1 ✉ , Nikolaus Ansorge2, Gleb Barmashenko3, Hans Bauer4, Christof Burkart5, Thomas Decker6, Thomas Ettrich 7, Ludwig Fischer von Weikersthal8, Thomas Geer9, Anke Gerhardt10, Sabine Höﬂing11, Lutz Jacobasch12, Michael Koenigsmann 13, Tobias Leidig 11, Ruben Plentz 14, Sebastian Räth3, Dietmar Reichert15, Markos Schulte 11, Nadine Schulte 16, Andreas Schwarzer17, Gabriele Siegler 18, Dirk Waldschmidt19 and Meinolf Karthaus20 © The Author(s) 2025 BACKGROUND: Not all patients with advanced pancreatic cancer (PC) proﬁt from 2nd-line chemotherapy. We evaluated predictive factors that are routinely collected during clinical care with the aim to support an informed and shared decision. METHODS: In a prospective study across 35 German sites, 151 patients with PC previously treated with gemcitabine/nab-paclitaxel were enrolled and 146 patients received biweekly nanoliposomal irinotecan/5-ﬂuorouracil/FA. We investigated whether time-totreatment-failure of 1st-line (TTF1) predicts 2nd-line treatment outcome. Patients were stratiﬁed into three equal cohorts based on TTF1 . Primary endpoint was TTF2, with secondary endpoints including overall survival (OS) and growth modulation index (GMI) . RESULTS: Median TTF2 was 3.71 months (95% CI 2.50–4.11) . Median OS was 7.72 months (95% CI 6.11–9.00) . TTF1 did not predict TTF2 or OS (HR 0.93, 95% CI 0.58-1.47 . Baseline parameters signiﬁcantly associated with TTF2 and OS included neutrophil count, CRP levels, and liver metastases, whereas ECOG performance score (PS) was primarily associated with OS and to a lesser extent with TTF2 . During treatment, patients with a CA 19-9 reduction of ≥25% had signiﬁcantly improved TTF2 and OS (p < 0.001) . CONCLUSION: TTF1 is not predictive of TTF2 or OS. Therefore, 2nd-line treatment should not be withheld irrespective of duration of TTF1 . CA 19-9 dynamics can be used to predict further beneﬁt to some extent. CLINICAL TRIAL REGISTRATION: EudraCT: 2016-005147-17; [ClinicalTrials.gov:](ClinicalTrials.gov:) NCT03468335. British Journal of Cancer (2026) 134:85–91; [https://doi.org/10.1038/s41416-025-03188-x](https://doi.org/10.1038/s41416-025-03188-x) BACKGROUND Ductal pancreatic adenocarcinoma (PC) is the ﬁfth leading cause of cancer-related deaths worldwide, with ~411,600 fatalities each year [1] . At diagnosis, less than 30% of patients qualify for a surgical resection, which is the only chance for cure. Median survival for patients with unresectable disease ranges from 8 to 12 months, with even lower survival for those with metastases. In selected patients, 1st-line systemic chemotherapy is well established. It prolongs median survival up to 11.1 months [2–4], and about 40–50% of these patients are still able to continue to 2ndline therapy [5] . Targeted treatment options are available for a small subset of patients after molecular proﬁling, with a high potential for future KRAS-directed therapies [6] . For advanced PC, 2nd-line chemotherapy with nanoliposomalirinotecan (Nal-IRI) in combination with 5-ﬂuorouracil (5-FU)/folinic acid (FA) increases median overall survival (OS) from 4.2 months to 6.1 months compared to 5-FU/FA alone [7] after failure of agemcitabine-based regimen. However, some grade 3/4 toxicities are reported (e.g. 13% diarrhoea and 14% fatigue) . A novel formulation of liposomal irinotecan/5-FU/FA showed similar results, with an OS of 7 .4 months (95% CI 6 .1–8.4) in the PANHEROIC-1 trial [8] . 1Caritasklinikum St. Theresia and Saarland University Medical Center, Saarbrücken and Homburg, Germany. 2St. Elisabeth-Krankenhaus, Köln, Germany. 3AIO-Studien-gGmbH, Berlin, Germany. 4Staburo GmbH, München, Germany. 5Schwarzwald-Baar-Klinikum Villingen-Schwe

FAQs

What was the main goal of the study in patients with advanced pancreatic adenocarcinoma?

To identify predictive factors, collected during routine clinical care, that can support informed decisions about 2nd-line chemotherapy outcomes.

Does time-to-treatment-failure of 1st-line therapy (TTF1) predict 2nd-line outcomes?

No. TTF1 did not predict 2nd-line TTF2 or overall survival (OS).

Which baseline factors were associated with TTF2 and OS?

Neutrophil count, CRP levels, and liver metastases were significantly associated with TTF2 and OS, while ECOG performance score was mainly associated with OS and to a lesser extent with TTF2.

Sep 29, 2026

Uploaded by Miles