Recent data indicated that the combination of neoadjuvant docetaxel, oxaliplatin, and S-1 followed by surgery and adjuvant S-1 was effective and tolerable in a population of Korean patients who had locally advanced gastric cancer.
A perioperative chemotherapy regimen consisting of neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 was well tolerated and effective in a population of Korean patients with resectable locally advanced gastric cancer (LAGC), according to data from the phase 3 PRODIGY study (NCT01515748).
After a median follow-up of 38.6 months (interquartile range, 23.5-62.1) and a total of 183 progression-free survival (PFS) events, PFS was found to be significantly superior in the S-1 plus surgery and adjuvant DOS chemotherapy (CSC) arm compared with the up-front surgery followed by adjuvant S-1 (SC) arm (HR, 0.70; 95% CI, 0.52-0.95; P = .023). The 3-year PFS rate was 66.3% (95% CI, 59.6%-72.1%) vs 60.2% (95% CI, 53.6%-66.3%) in the CSC and SC groups, respectively.
“The phase 3 PRODIGY study has shown the benefit of adding neoadjuvant chemotherapy to standard D2 surgery plus adjuvant chemotherapy in Asian patients with resectable LAGC,” wrote the investigators. “The study met its primary end point: PFS was statistically significantly improved in CSC- versus SC- treated patients and HRs favored CSC in most subgroups.”
The research included 530 patients in the intent-to-treat population across 18 Korean hospitals between January 18, 2012, and January 2, 2017. Of this cohort, 266 patients were randomized to the CSC arm and 264 to the SC arm.
Overall, 89.9% of patients in the CSC group received all 3 cycles of DOS. Moreover, 16 patients who began neoadjuvant chemotherapy did not undergo surgery, with reasons including consent withdrawal (n = 6), death (n = 4), progressive disease (PD; n = 3) during neoadjuvant therapy (n = 3), lost to follow-up (n = 2), or adverse effects (AEs) before surgery (n = 1). From study enrollment to surgery, the median time between was 11.6 and 1.9 weeks in the CSC and SC groups, respectively.
Unlike PFS, the overall survival (OS) rate was not statistically significantly better for patients in the CSC group compared with those in the SC group (HR, 0.84; 95% CI, 0.60-1.19; P = .338). Expanded to 3-years, the OS rate was 74.2% (95% CI, 67.7%-79.6%) and 73.4% (95% CI, 67.0%-78.7%) in the CSC and SC groups, respectively.
Patients eligible for enrollment were between the ages of 20 to 75 years with an ECOG performance status of 0 to 1 and histologically confirmed primary locally advanced gastric or gastroesophageal junction adenocarcinoma amenable to curative resection.
Patients in the CSC group began treatment within 7 days of randomization, which included docetaxel at 50 mg/m2, oxaliplatin at 100 mg/m2 intravenously on day 1, and S-1 at 40 mg/m2 orally twice a day on days 1 through 14 every 3 weeks for 3 cycles.
A limitation of the data centered around the small HRs for both the PFS and absolute PFS data, with OS data also being immature. Moreover, other neoadjuvant chemotherapy options need to be explored outside of the treatment within PRODIGY.
“This trial establishes perioperative chemotherapy as an appropriate new standard-of-care option for patients with LAGC in Asia, analogous to the therapeutic approach commonly used in Western countries,” the investigators concluded.
Kang YK, Yook JH, Park YK, et al. PRODIGY: A phase III study of neoadjuvant docetaxel, oxaliplatin, and S-1 plus surgery and adjuvant S-1 versus surgery and adjuvant S-1 for resectable advanced gastric cancer. J Clin Oncol. Published online ahead of print, June 16, 2021. doi:10.1200/JCO.20.02914