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

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. 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-to-treatment-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). 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). 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. EudraCT: 2016-005147-17; ClinicalTrials.gov: NCT03468335.