S-1/Chemo Regimen Improves PFS in Resectable Advanced Gastric Cancer

"Neoadjuvant [docetaxel, oxaliplatin, and S-1] chemotherapy, as part of perioperative chemotherapy, prolonged the OS of Asian patients with [locally advanced gastric cancer] relative to patients treated with surgery and adjuvant S-1," according to the study authors.

Neoadjuvant treatment with docetaxel, oxaliplatin, and S-1 followed by surgery and then adjuvant S-1 was found to improve progression-free survival (PFS) and overall survival (OS) compared with surgery followed by adjuvant S-1 in patients with resectable locally advanced gastric cancer who have clinical T2 to 3N+ or T4Nany disease, according to long-term follow-up data from the phase 3 PRODIGY trial (NCT01515748) published in the Journal of Clinical Oncology.¹

Neoadjuvant chemotherapy plus S-1 and adjuvant therapy significantly improved PFS with a 30% reduction in the risk of disease progression or death compared with the adjuvant regimen alone in this patient population (HR, 0.70; 95% CI, 0.53-0.94; stratified log-rank P = .016).

Results also showed that the neoadjuvant addition led to a 28% reduction in the risk of death vs adjuvant therapy alone (HR, 0.72; 95% CI, 0.54-0.96; stratified log-rank P = .027); the 8-year OS rates were 63.8% (95% CI, 57.9%-70.3%) and 54.6% (95% CI, 48.6%-61.4%), respectively.

“Neoadjuvant [docetaxel, oxaliplatin, and S-1] chemotherapy, as part of perioperative chemotherapy, prolonged the OS of Asian patients with [locally advanced gastric cancer] relative to patients treated with surgery and adjuvant S-1,” lead study author Yoon-Koo Kang, MD, of the Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, in the Republic of Korea, and coinvestigators wrote in the publication.¹ “It should be considered one of the standard treatment options for patients with [locally advanced gastric cancer] in Asia.”

Adjuvant regimens vary by geographic populations, the authors noted. In Asia, specifically, D2 gastrectomy followed by adjuvant chemotherapy is a standard of care for this population vs perioperative chemotherapy in Western countries.

In PRODIGY, 530 patients were randomly assigned to receive the neoadjuvant/adjuvant regimen (n = 264) or the adjuvant regimen alone (n = 266), which comprised the intent-to-treat population. Forty-six patients were then excluded and narrowed down the set to 246 and 238 patients in full analysis set, respectively.

Regarding baseline characteristics in the adjuvant therapy–alone group and neoadjuvant/adjuvant group, the median age was 58 years (51-64) in both; 81.3% and 77.3% were male, respectively; 28.0% and 37.4% had an ECOG performance status of 1, 96% and 92% had gastric cancer as their primary tumor location; most patients had T4a stage disease at 64.6% and 61.3%; 49.2% and 48.3% had N2 stage disease; and 37.0% and 35.7% of patients had stage IIIB disease.

Previously, 5-year OS rates were 66.8% (95% CI, 61.1%-73.1%) with neoadjuvant therapy vs 63.0% (95% CI, 57.3%-69.3%) with adjuvant therapy alone.²

The primary end point was PFS, with OS as a secondary end point. The data cutoff date was September 2022, with a median follow-up duration of 99.5 months (range, 68.6-127.4).

There were a total 36.6% of deaths (n = 87) in the neoadjuvant/adjuvant arm vs 45.1% (n = 111) in the adjuvant alone arm. The findings in the ITT population were consistent with the overall findings, the authors noted.

Data also showed that the OS and PFS benefits with the addition of neoadjuvant treatment was more pronounced in those with cT4Nany tumors (HR, 0.69) and those with cT4N+ tumors (HR, 0.70).

“Therefore, neoadjuvant chemotherapy may be preferentially considered for patients with cT4 disease in Asian populations. This is in contrast to the Western circumstances, where perioperative chemotherapy is recommended for ≥cT2 or cN1 tumors,” the authors concluded.

References

1. Kang Y-K, Kim H-D, Yook JH, et al. Neoadjuvant docetaxel, oxaliplatin, and S-1 plus surgery and adjuvant S-1 for resectable advanced gastric cancer: updated overall survival outcomes from phase III PRODIGY. J Clin Oncol. Published online July 12, 2024. doi:10.1200/JCO.23.02167
2. Kang Y-K, Yook JH, Park Y-K, 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. 2021;39(26):2903-2913. doi:10.1200/JCO.20.02914