KEY TAKEAWAYS
- The TOPGEAR phase II & III trial aimed to assess if adding preop CRT to periop CT improves outcomes in resectable gastric cancer.
- The primary endpoint was to determine OS.
- The preop CRT improves pathological outcomes but does not enhance OS compared to periop CT alone.
In Western countries, resectable gastric cancer is usually treated with perioperative chemotherapy (periop CT). There is interest in adding preoperative chemoradiotherapy (preop CRT), but it has not been compared to perioperative CT alone.
Trevor Leong and the team aimed to verify if adding preop CRT to periop CT improves pathological complete response (pCR) and overall survival (OS) compared to perioperative CT alone.
The TOPGEAR phase 3 trial randomly assigned patients with resectable stomach and gastro-esophageal junction adenocarcinoma to receive either periop CT or with preop CRT. The CT-only group received either 3 cycles of epirubicin/cisplatin/5-fluorouracil (ECF) or 4 cycles of fluorouracil/leucovorin/oxaliplatin/docetaxel (FLOT) before and after surgery.
The preop CRT group received 1 less cycle of preop chemotherapy, followed by CRT (45 Gy radiation plus infusional 5-FU) and then the same postoperative CT. The primary endpoint was OS, whereas pFS, pCR rates, toxicity, and quality of life were secondary goals.
The results showed that between September 2009 and May 2021, 574 patients from 70 sites across Australasia, Europe, and Canada were enrolled. Of all the patients, 288 were randomized to the perioperative CT group, and 286 were randomized to the preoperative CRT group.
The patients receiving preoperative CRT had a higher pCR rate (16.7% vs. 8.0%), a better major pathological response rate (49.5% vs. 29.3%), and more tumor downstaging. After a median follow-up of 66.7 months, OS and pFS were similar.
The median OS was 49.4 months for periop CT vs. 46.4 months for preop CRT, and the median PFS was 31.8 months for periop CT vs. 31.4 months for preop CRT. Preop CRT did not lead to more treatment toxicity or surgical complications.
The study concluded that while preoperative CRT improves pathological outcomes, it does not enhance OS compared to periop CT alone in patients with resectable gastric and gastro-esophageal junction adenocarcinoma.
The trial was sponsored by Australasian Gastro-Intestinal Trials Group.
Source: https://cslide.ctimeetingtech.com/esmo2024/attendee/confcal/show/session/43
Clinical Trial: https://clinicaltrials.gov/study/NCT01924819
Leong T, Smithers BM, Michael M, et al. (2024). “A randomized phase III trial of perioperative chemotherapy (periop CT) with or without preoperative chemoradiotherapy (preop CRT) for resectable gastric cancer (AGITG TOPGEAR): Final results from an intergroup trial of AGITG, TROG, EORTC and CCTG.” Presented at ESMO 2024 (Abstract LBA58).
