Determinants of eligibility for second-line chemotherapy following gemcitabine plus nab-paclitaxel therapy in patients with unresectable pancreatic cancer: A retrospective study

Background: Second-line chemotherapy (2L) is recommended after gemcitabine plus nab-paclitaxel (GnP) first-line chemotherapy (1L) for unresectable pancreatic cancer (UR-PC). However, in routine clinical practice, not all patients proceed to 2L. This retrospective study aimed to identify baseline clinical and biological factors associated with 2L eligibility. Methods: We retrospectively reviewed the data of 124 consecutive patients with UR-PC who received 1L GnP between 2016 and 2024 at a single center, excluding those with postoperative recurrence. Patients were grouped by 2L receipt [2L(+), n = 63] or non-receipt [2L(−), n = 61]. Overall survival (OS) and progression-free survival (PFS) from 1L (baseline) were assessed by Kaplan–Meier and Cox regression analyses. Predictors of 2L eligibility were evaluated by logistic regression. Results: The 2L(+) group less frequently had baseline ascites and better Eastern Cooperative Oncology Group performance status. Median OS was 15.5 vs. 4.7 months (p < 0.001) and median PFS was 5.9 vs. 3.0 months (p = 0.004) for 2L(+) vs. 2L(−). Multivariate Cox analysis identified 2L (hazard ratio [HR] 0.262), disease control (HR 0.398), and neutrophil-to-lymphocyte ratio (HR 0.530) as independent factors for longer OS. Multivariate logistic regression revealed that the absence of ascites independently predicted 2L eligibility (adjusted odds ratio 4.435, 95% confidence interval 1.583−12.423, p = 0.005). Conclusions: Baseline ascites was a barrier to 2L initiation after 1L GnP in patients with UR-PC. Nevertheless, 2L was associated with improved survival regardless of ascites status. This supports individualized reassessment and proactive supportive care to maximize opportunities for sequential chemotherapy.