In the Korean phase III PRODIGY trial reported in the Journal of Clinical Oncology, Yoon-Koo Kang, MD, and colleagues found that the addition of neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) to D2 gastrectomy followed by adjuvant S-1 was associated with improved progression-free survival in patients with resectable locally advanced gastric cancer.
Yoon-Koo Kang, MD
Study Details
In the multicenter open-label trial, a total of 484 patients with gastric or gastroesophageal junction adenocarcinoma (clinical TNM staging = T2–3N1 or T4Nany) in the full-analysis set were randomly assigned between January 2012 and January 2017 to receive neoadjuvant chemotherapy, D2 surgery, and adjuvant S-1 (CSC group, n = 238) or D2 surgery and adjuvant S-1 (SC group, n = 256). The full-analysis set consisted of all patients starting neoadjuvant therapy in the CSC group and all those undergoing surgery in the SC group. Neoadjuvant DOS consisted of docetaxel at 50 mg/m2 and oxaliplatin at 100 mg/m2 on day 1, as well as oral S-1 at 40 mg/m2 twice daily on days 1 to 14 every 3 weeks for three cycles. Adjuvant S-1 was given at 40 to 60 mg based on body surface area twice daily on days 1 to 28 every 6 weeks for eight cycles. The primary endpoint was progression-free survival.
Progression-Free Survival
At data cutoff (January 2019), median follow-up was 38.6 months (interquartile range = 23.5–62.1 months). In the full-analysis set, the CSC group had improved progression-free survival vs the SC group, with a hazard ratio [HR] of 0.70 (95% confidence interval [CI] = 0.52–0.95, P = .023) after adjustment for the stratification factors of study site and clinical TNM staging. Progression-free survival at 3 years was 66.3% (95% CI = 59.6%–72.1%) vs 60.2% (95% CI = 53.6%–66.3%).
Sensitivity analyses supported these findings in the intent-to-treat population consisting of 266 CSC patients and 264 SC patients (HR = 0.69, 95% CI = 0.51–0.93, P = .016) and in a 6-month landmark analysis (HR = 0.74, 95% CI = 0.54–1.00, P = .043).
At time of analysis, CSC was not associated with significantly improved overall survival (HR = 0.84, 95% CI = 0.60–1.19, P = .338), with 3-year rates of 74.2% (95% CI = 67.7%–79.6%) vs 73.4% (95% CI = 67.0%–78.7%).
KEY POINTS
- The addition of neoadjuvant chemotherapy to surgery and adjuvant S-1 improved progression-free survival.
- No difference in overall survival has been observed.
Adverse Events
During neoadjuvant chemotherapy, grade ≥ 3 adverse events included neutropenia (12.6%), febrile neutropenia (9.2%), and diarrhea (5.0%). Adverse events led to death in two patients, due to febrile neutropenia and dyspnea. Surgery-related complications were uncommon, with no differences between groups in incidence of complications or length of hospital stay. One surgery-related death (due to pulmonary embolism) occurred in a patient in the CSC group. During adjuvant therapy, the most common grade ≥ 3 adverse event was neutropenia (6.4% in CSC group vs 5.3% in SC group; febrile neutropenia occurred in 0 vs 1 patient). No treatment-related deaths occurred during adjuvant chemotherapy.
The investigators concluded, “PRODIGY showed that neoadjuvant DOS [docetaxel, oxaliplatin, and S-1] chemotherapy, as part of perioperative chemotherapy, is effective and tolerable in Korean patients with locally advanced gastric cancer.”
Dr. Kang, of Asan Medical Center, University of Ulsan College of Medicine, Seoul, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Sanofi-Aventis, Taiho Pharmaceutical, and Jeil Pharmaceutical Co, Ltd. For full disclosures of the study authors, visit ascopubs.org.
