The benefit of adjuvant chemotherapy following pancreaticoduodenectomy for pancreatic adenocarcinoma depends on response to neoadjuvant therapy

Abstract

Presenter: Patrick McCarthy MD | Brooke Army Medical Center Background: Neoadjuvant therapy (NT) is increasingly offered to patients with pancreatic ductal adenocarcinoma (PDAC) who may undergo resection. However, it remains unclear which patients who have received NT and surgical resection should receive additional adjuvant therapy (AT). We sought to determine which patients benefit from further AT following NT and pancreatectomy. Methods: The 2004-2017 National Cancer Database was queried for patients with non-metastatic PDAC who received NT followed by pancreaticoduodenectomy. Only patients with reported data regarding receipt of AT were included. Patients were categorized by their change from clinical to pathologic stage; if pathologic stage (T, N, or overall) was lower than their clinical stage, they were considered downstaged. We then classified patients as to whether they had nodal down-staging specifically, or any downstaging (T, N, or overall). Propensity score weighting according to demographics, treatment location, tumor stage, grade, location, and readmission rate was used with generalized boosted models to adjust for pretreatment covariate imbalance between the treatment groups. Weighted Kaplan-Meir method was used to estimate the cumulative survival with weighted log-rank test to compare the staging groups. Results: A total of 2,901 patients were identified, of which 1,102 (38.0%) patients received AT and 1,799 (62.0%) did not receive AT. On final pathology, 1,427 patients (49.1%) were pathologically node negative and 125 patients (4.3%) had a pathologic complete response. With regard to downstaging, 312 patients (10.8%) achieved nodal downstaging and 822 (28.3%) patients achieved any downstaging. In all patients that received NT, the group that received AT had a significantly improved overall survival (OS) (p=0.002). When stratified by final nodal status, patients receiving AT had improved survival amongst node positive patients (p=0.002), and node negative patients (p=0.012). For patients without downstaging, those who received AT had improved OS (nodal down-staging: p=0.002; any downstaging: p<0.001, respectively). In patients with downstaging after NT, however, those receiving AT did not have improved survival with nodal downstaging (p=0.128) or any downstaging (p=0.323). Conclusion: Response to NT appears to determine benefit attained from the addition of AT following pancreaticoduodenectomy for PDAC; patients who have a favorable response to NT may not benefit from additional chemotherapy. Future trials should examine the relationship between tumor regression after NT and benefit from AT, including regimens identical to and different from the patient’s NT regimen. Additionally, this analysis calls for future randomized trials examining the benefit of AT in patients who have had significant response to NT.