Adjuvant chemotherapy and outcome in patients (pts) with nodal (N-) and resection margin negative (R0) pancreatic adenocarcinoma (PC): A systematic review and meta-analysis

Background: Adjuvant chemotherapy following PC resection improves overall survival (OS). It is uncertain whether benefit is influenced by nodal and resection status or other factors. Methods: A systematic review of electronic databases identified published phase 2/3 studies investigating use of adjuvant chemotherapy in pts with resected PC. Efficacy (disease-free survival [DFS], OS, 5 yr OS) was explored using meta-analysis. Subgroup analysis explored effects based on nodal/resection status. Meta-regression also explored influence of age, gender, performance status [PS] and proportion of pts with head of pancreas (HOP) tumors on benefit of adjuvant chemotherapy. Results: Ten studies comprising 3644 pts were included. Two prospective phase 2 studies; 8 phase 3 trials. Median age was 63 yrs (range 24-84), 46% male. In 2268 pts with PS reported; 42% were PS 0, 51% PS 1. Tumor location was reported in 719 pts; 82% had HOP tumors. Of 3524 pts with available data; 33% N- and 67% R0. Overall, in studies of experimental vs control, adjuvant therapy significantly improved DFS (HR 0.67, CI 0.48-0.93, P = 0.02), OS (HR 0.77, 95% CI 0.68-0.87, P < 0.001) and odds of death risk at 5 yrs (OR 0.53, 95% CI 0.41-0.70, P < 0.001). In studies comparing chemotherapy to surgery only, adjuvant therapy also significantly improved DFS (HR 0.57, 95% CI 0.49-0.76, P < 0.001) and OS (HR 0.74, 95% CI 0.64-0.87, P < 0.001). There was a numerical but non-significant greater effect of adjuvant therapy in N- vs N+ pts (HR 0.58 vs 0.71, P for difference = 0.29). There was no difference in effect between pts with R0 or R1 disease (HR 0.70 vs 0.69, P for difference = 0.95). There was greater OS benefit from adjuvant therapy in pts with PS 0 (P = 0.04) and significantly less benefit on 5 yr OS in pts with HOP tumors (P = 0.04). Conclusions: The relative benefit of adjuvant chemotherapy seems similar in N-/N+ and in R0/R1 pts. This will translate into greater absolute benefit in the N+ and R1 pts due to their greater absolute risk of recurrence/death. Adjuvant chemotherapy is recommended for all pts with resected PC, where clinically appropriate, and greater benefit was seen in pts with PS 0 and body/tail tumors.