Elucidating the Causes of Improved Survival in Clinical Trials of Randomized Adjuvant Pancreatic Ductal Adenocarcinoma (PDAC).

BACKGROUND: Overall survival (OS) has increased in recent adjuvant clinical trials of pancreatic ductal adenocarcinoma (PDAC). Although oncologists have taken notice, the root causes have not been fully examined.
METHODS: All phase 3 adjuvant PDAC clinical trials were screened (n = 13), and eight trials (2007-2019) that met a study requirement of having a gemcitabine monotherapy arm to serve as a uniform comparative anchor across trials were identified. Patient enrollment eligibility criteria were compared across trials and categorized as tumor- or patient-related factors. Disease-free survival (DFS) and OS in the gemcitabine-only and non-gemcitabine arms were plotted and compared over time using linear regression.
RESULTS: In the non-gemcitabine arms, OS increased over time, but the slope did not achieve statistical significance (p = 0.0815). Interestingly, OS improved for patients receiving only gemcitabine (slope, 1.99 months; p = 0.0018), whereas DFS remained constant (p = 0.897). Carbohydrate antigen (CA) 19-9 values and pathologic profiles of tumors were only marginally different across all cohorts. Recent adjuvant trials had stricter inclusion criteria (i.e., more patients were excluded for medical reasons; linear regression, p = 0.010).
CONCLUSION: Survival for patients with resected PDAC has roughly doubled in phase 3 adjuvant trials during the past decade. Improved outcomes likely are attributable to improved adjuvant therapeutic regimens, but also reflect healthier patients enrolled in the more recent trials.