TOPGEAR (EORTC-22114-40111-GITCG-ROG) Trial

Design - Phase 3 intergroup: preop chemoradiation + perioperative chemo (Arm B) vs perioperative chemo alone (Arm A, ECF or FLOT), resectable gastric/GEJ adenocarcinoma (NCT01924819), N=574; primary OS.

OS (primary, NEGATIVE) - Median 46 vs 49 mo; HR 1.05 (95% CI 0.83-1.31); 5-year OS ~45% in both arms - no survival benefit from adding chemoradiation.

pCR - Improved with chemoradiation (17% vs 8%) but did not translate into an OS benefit.

Safety - Both arms well tolerated; chemoradiation did not increase treatment-related toxicity or surgical risk (compliance 95% RT, 91% chemo; R0 92% both arms).

Regulatory - Investigational/academic - no FDA approval implication; consolidates perioperative chemotherapy (e.g., FLOT) as standard, without routine preoperative chemoradiation.

Sponsor - AGITG with EORTC, TROG, CCTG intergroup.

Compiled and reviewed by the KOL Pulse research team, led by Brian Shields, Founder, KOL Pulse. Last updated July 21, 2026.

Overall Survival — Primary Endpoint

Median: 46 months (preop CRT + perioperative chemo (Arm B)) vs. 49 months (perioperative chemo alone (Arm A, ECF or FLOT)). HR 1.05 (95% CI 0.83-1.31) 5-year OS rate rate: 45% (CRT + chemo) vs. 45% (chemo alone). Phase 3 intergroup trial enrolled N=574 (Arm A chemo alone 288, Arm B CRT + chemo 286). Tumor location: 35% at GEJ; Stage: 88% T3, 60% node-positive. Median follow-up 67 months. Median OS 46 months (CRT) vs. 49 months (chemo alone) — HR 1.05 (95% CI 0.83-1.31) — NOT significantly different. 5-year OS ~45% in both groups. Median PFS 31 vs. 32 months. Primary endpoint NOT MET. Leong et al., NEJM 2024.

Overall Survival (OS)

HR 1.05 (95% CI 0.83-1.31) OS was the primary endpoint (see above). Despite pCR improvement with CRT (17% vs. 8%), no OS difference. Investigators concluded preoperative CRT should NOT become routine SOC. Consolidates perioperative chemotherapy (FLOT, per ESOPEC for esophageal; FLOT4 for gastric) as SOC.

Safety & Tolerability

Both arms well-tolerated and feasible. Addition of CRT did not increase treatment-related toxicity or surgical risks. Compliance 95% RT, 91% chemo. Surgery performed 84% (CRT) vs. 89% (chemo alone). R0 resection 92% in both. pCR 17% vs. 8% (significantly better with CRT) but no OS translation. Toxicity: similar across groups, no major increase in surgical or GI/hematologic toxicities.

Clinical Implications

❌ Negative Phase 3: Preoperative CRT adds no OS benefit to perioperative chemo in resectable gastric/GEJ cancer. TOPGEAR is the definitive Phase 3 answer to whether preoperative chemoradiation improves outcomes over perioperative chemotherapy alone in resectable gastric/GEJ adenocarcinoma. Despite more than doubling pCR (17% vs. 8%) and more tumor/node downstaging, the addition of 45 Gy preoperative CRT did NOT improve OS (46 vs. 49 months) or PFS (31 vs. 32 months). Along with ESOPEC (FLOT > CROSS in esophageal adenocarcinoma), TOPGEAR consolidates perioperative chemotherapy (FLOT) as SOC globally. Role of radiation in this setting is retreating; future direction focuses on improving systemic regimens with immunotherapy (MATTERHORN perioperative durvalumab + FLOT) and targeted agents.

What is the TOPGEAR trial?

TOPGEAR (EORTC-22114-40111-GITCG-ROG) is a Phase 3 intergroup randomized trial (NCT01924819) that tested whether adding preoperative chemoradiotherapy to perioperative chemotherapy improves outcomes in resectable gastric or gastroesophageal junction adenocarcinoma. Arm B received preoperative chemoradiation plus perioperative chemotherapy, and Arm A received perioperative chemotherapy alone (ECF or FLOT), with overall survival as the primary endpoint.

Did TOPGEAR meet its primary endpoint?

No. TOPGEAR was a negative trial. Median overall survival was 46 months with preoperative chemoradiation plus chemotherapy versus 49 months with chemotherapy alone (HR 1.05; 95% CI 0.83-1.31), and 5-year overall survival was about 45% in both arms - no survival benefit from adding chemoradiation.

If chemoradiation improved pathologic complete response, why didn't survival improve?

Preoperative chemoradiation did significantly increase the pathologic complete response rate (17% versus 8%), but this did not translate into longer overall survival. The investigators concluded that preoperative chemoradiotherapy should not become routine standard of care in resectable gastric/GEJ cancer.

Does TOPGEAR change the standard of care?

TOPGEAR consolidates perioperative chemotherapy (such as FLOT) as the standard for resectable gastric/GEJ adenocarcinoma and argues against routinely adding preoperative chemoradiation. There is no drug approval involved; this is a treatment-strategy comparison that informs multidisciplinary practice.

Was adding radiotherapy safe in TOPGEAR?

Yes. Both arms were well tolerated and feasible. Adding chemoradiation did not increase treatment-related toxicity or surgical risk; compliance was 95% for radiotherapy and 91% for chemotherapy, surgery was performed in the large majority of patients, and R0 resection was achieved in 92% of both arms.