In a retrospective cohort study reported in the Journal of Clinical Oncology, Habib et al found that adjuvant chemotherapy benefited some groups of patients with resected intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC), but that overtreatment and undertreatment occurs in a substantial proportion of patients.
As stated by the investigators, “The benefit of adjuvant therapy for … IPMN-derived … PDAC remains unclear because of severely limited evidence. Although biologically distinct entities, adjuvant therapy practices for IPMN-derived PDAC are largely founded on pancreatic intraepithelial neoplasia-derived PDAC. We aimed to evaluate the role of adjuvant chemotherapy in IPMN-derived PDAC.”
Study Details
The study involved data from patients at 16 centers in the international Verona IPMN Consortium treated from 2005 to 2018. CA19-9 was elevated in 54.9% of patients, and 43.6% had node-positive disease. The primary outcome measure was the effect of adjuvant chemotherapy on overall survival.
Key Findings
Among 1,031 patients included in the analysis, 63.5% received adjuvant chemotherapy. In the total population, factors associated with poorer overall survival included nodal disease (hazard ratio [HR] = 2.88, P < .001) and elevated (≥ 37 to < 200 μ/mL; HR = 1.44, P = .006) or markedly elevated (≥ 200 μ/mL; HR= 2.53, P < .001) CA19-9 levels. Adjuvant chemotherapy therapy was associated with improved overall survival (HR = 0.66, 95% confidence interval = 0.46–0.95).
A 34.4-month improvement in median overall survival was observed in patients with node-positive disease and elevated CA19-9 who received adjuvant chemotherapy (P = .047), and a median 12.6-month improvement was observed in those with node-positive disease and markedly elevated CA19-9 (P < .001). No overall survival benefit with adjuvant chemotherapy was observed in node-negative patients, irrespective of normal, elevated, or markedly elevated CA19-9 levels (all P > .05).
Based on a model constructed by the investigators, adjuvant chemotherapy undertreatment occurred in 18.1% of patients and overtreatment in 61.2%. The factors associated with adjuvant chemotherapy administration included younger age, R1 resection margin, poorer differentiation, and nodal disease.
The investigators concluded: “Almost half of patients with resected IPMN-derived PDAC may be overtreated or undertreated. In patients with node-negative disease or normal CA19-9, adjuvant chemotherapy is not associated with a survival benefit, whereas those with node-positive disease and elevated CA19-9 have an associated benefit from adjuvant chemotherapy. A decision tree was proposed. Randomized controlled trials are needed for validation.”
Christopher L. Wolfgang, MD, PhD, of New York University Grossman School of Medicine, New York, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: For full disclosures of the study authors, visit ascopubs.org.
