2019 GI Cancers Symposium: Neoadjuvant Chemotherapy vs Upfront Surgery in Resectable Pancreatic Cancer
A phase II/III trial presented by Unno et al at the 2019 Gastrointestinal Cancers Symposium (Abstract 189) sought to compare neoadjuvant chemotherapy (using gemcitabine and the oral fluoropyrimidine combination of tegafur/gimeracil/oteracil [S-1]) to upfront surgery in patients with histologic confirmation of resectable pancreatic ductal adenocarcinoma.
Study Methods
Patients were randomly assigned to be treated with two cycles of neoadjuvant chemotherapy—with 1 g/m2 of gemcitabine on days 1 and 8 and 40 mg/m2 of oral S-1 twice daily on days 1 to 14—or undergo upfront surgery. Adjuvant S-1 was administered for 6 months for patients with curative resection and full recovery within 10 weeks after surgery in both arms.
In the phase III trial, the primary endpoint was overall survival. Secondary endpoints included adverse events, resection rate, recurrence-free survival, residual tumor status, nodal metastases, and tumor marker kinetics.
Over the course of 3 years, 364 patients were enrolled in 57 centers—182 were randomly assigned to receive neoadjuvant chemotherapy and 182 were randomly assigned to receive upfront surgery. A total of 362 patients were included in the intention-to-treat analysis.
Study Findings
Median overall survival was 36.7 months in the neoadjuvant chemotherapy group and 26.6 months in the upfront surgery group (hazard ratio = 0.72, 95% confidential interval 0.55–0.94; P = .015 [stratified log-rank test]).
In the neoadjuvant chemotherapy group, the most commonly reported grade 3/4 adverse events were leukopenia and neutropenia (72.8%). The resection rate, R0 resection rate, and surgical morbidity were equivalent in the two groups. Additionally, neither group had any perioperative mortality.
The investigators concluded, “This phase III study demonstrated the significant survival benefits of [neoadjuvant chemotherapy with gemcitabine and S-1]. Therefore, the results indicated that neoadjuvant chemotherapy could be a new standard for patients with resectable pancreatic ductal adenocarcinoma.”
Disclosure: The study authors' full disclosures can be found at coi.asco.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
