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.