The earlier the better.

Top Line: Peri-operative chemo is the preferred approach for locally advanced gastric cancer, but does that approach also work best when using S-1 chemotherapy in Asian patients?

The Study: In East Asian countries, adjuvant S-1 is a standard approach for LAGC. So, let’s talk about S-1. No, not voting rights, we’re not going there. We’re talking about the systemic therapy that combines tegafur (fluorouracil prodrug), gimeracil (dihydropyrimidine dehydrogenase inhibitor that blocks fluorouracil degradation), and oteracil (blocks fluorouracil conversion in the gut). It’s not available in the US, and it’s felt that S-1 isn’t as well tolerated in Western populations due to CYP2A6 polymorphisms that lead to increased 5-FU concentrations and lower tolerable dose. Two recent trials have asked whether peri-operative S-1 based chemo is superior to adjuvant therapy alone. In PRODIGY, over 500 Korean patients with resectable LAGC were randomized to surgery followed by adjuvant S-1 or neoadjuvant docetaxel, oxaliplatin, and S-1 (think FLOT) followed by surgery and then adjuvant S-1. Neoadjuvant therapy significantly improved PFS with a 3-year PFS rate of 66% vs 60%, but there was no difference in OS. In RESOLVE, over 1000 Chinese patients with LAGC were randomized to 1) peri-operative S-1 and oxaliplatin SOX, 2) adjuvant SOX, or 3) adjuvant CapeOX. Compared to adjuvant CapeOX, peri-op SOX improved 3-year DFS from 51→ 59%. In addition, adjuvant SOX was non-inferior to CapeOX with a 3-year DFS rate of 57%.

TBL: Peri-operative S-1 based combination chemotherapy improves PFS/DFS compared to adjuvant S-1 monotherapy and adjuvant CapeOX in Asian patients with LAGC. | Kang, J Clin Oncol 2021 and Zhang, Lancet Oncol 2021