Prediction of Early Treatment Failure of Second-Line Nal-Iri/5-fu/fa in Patients with Advanced Pancreatic Adenocarcinoma (AIO-PAK-0216).

721 Background: Second-line Nal-Iri/5-Fluorouracil/Folinic Acid (Nal-Iri/5-FU/LV) increases overall survival of unselected patients (pts) with metastatic pancreatic ductal adenocarcinoma (PDAC) after gemcitabine-based therapy. It is unknown, which pts will likely benefit or could probably profit more from alternative approaches. Methods: In this prospective trial, 156 pts with locally advanced or metastatic PDAC were included for treatment with biweekly Nal-Iri/5-FU/LV (70 mg/m², 2.4 g/m², 400 mg/m²) after failure of 1st line chemotherapy with Gemcitabine/nab-Paclitaxel, with comprehensive evaluation of prior treatment characteristics, potential predictive factors, and quality of life. Primary end point is the correlation of time to treatment failure (TTF) of 1st and 2nd line therapy. Moreover, translational research was done to measure and evaluate biomarkers in blood and tumor tissue. Here, we explore patient characteristics in two subgroups with short or long treatment duration, with the aim to evaluate potential predictive factors for further analysis. Results: 139 (90%) of the 156 pts included between 03/2018 and 07/2021 in 40 German sites received medication. End of treatment is documented for 128 pts, with 5 still on treatment as of 05/2022 Mean (±SD) treatment duration was 15.5 weeks or 7.7±7.1 cycles (median 7 weeks; 5 cycles). 37 (25%) pts received ≥ 10 cycles. The median was used to separate two subgroups of short and long treatment duration (STD, ≤ 5 cycles, n=66 (52%) vs. LTD, > 5 cycles, n=62, (48%)). Reasons for treatment discontinuation clearly differed between the two subgroups: death in 9% vs. 3%, toxicity in 9% vs. 2%, unrelated medical condition in 12% vs. 2%, and progressive disease in 46% vs. 73%, respectively. Investigator´s decision was a reason for discontinuation in 6% vs. 5%. Pts with STD had a lower performance status (ECOG 1 or 2 in 74% vs. 52%, ECOG 0 in 20% vs. 44% in STD vs. LTD group), lower albumin levels (below normal in 36% vs. 24.2%) and were more likely to suffer from liver metastases (overall 82% vs. 66%). There were no relevant differences with regard to age, sex and tumor burden (number of metastases or CA19-9 levels). Conclusions: Early treatment discontinuation was primarily associated with patient-related factors such as low performance status, low albumin levels and comorbidities, characteristics which could be used to spare patients from treatment with an unfavorable risk-to-benefit ratio. In contrast, surrogate markers for tumor burden did not correlate with treatment success. Clinical trial information: NCT03468335 .