Does Adding Preoperative CRT to Perioperative Chemotherapy Improve Survival for Resectable Gastric Cancer?

While improving pathological outcomes, the addition of preoperative chemoradiotherapy (CRT) to perioperative chemotherapy may not have added overall survival (OS) benefit for patients with resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma, according to new research presented as a late-breaking abstract at the European Society for Medical Oncology Congress 2024.

Perioperative chemotherapy is considered standard of care for resectable gastric/GEJ adenocarcinoma. Further research is needed on the effects of adding preoperative CRT to this management approach.

Dr. Trevor Leong and colleagues designed the TOPGEAR study to determine whether the addition of preoperative CRT to perioperative chemotherapy would improve pathological complete response (pCR) rates and OS compared to perioperative chemotherapy alone. The international phase 3 trial randomized 574 patients across 70 international sites from September 2009 to May 2021.

A total of 286 patients received preoperative CRT and 288 received perioperative chemotherapy. The perioperative chemotherapy group received three cycles of epirubicin/cisplatin/5-fluorouracil (ECF) or four cycles of fluorouracil/leucovorin/oxaliplatin/docetaxel (FLOT) both pre- and post-operatively.

The preoperative CRT group received one less cycle of preoperative chemotherapy followed by chemoradiotherapy (45 Gy in 25 fractions radiation plus infusional 5-FU), followed by the same postoperative chemotherapy.

The primary endpoint was OS. Secondary endpoints included progression-free survival (PFS), pCR rates, toxicity, and quality of life.

Dr. Leong and colleagues found that patients in the preoperative CRT arm achieved a higher pCR  rate (16.7% vs 8.0%, respectively), a higher rate of major pathological response (0% to less than 10% residual tumor: 49.5% vs 29.3%, respectively), and greater tumor downstaging following resection.

However, after a median follow-up of 66.7 months, no significant difference in OS or PFS was found. The median OS was 46.4 months versus 49.4, respectively, and the median PFS was 31.4 months versus 31.8 months, respectively.

Researchers noted that preoperative CRT was not associated with increased perioperative treatment toxicity or a higher rate of surgical complications.

“Despite improving pathological outcomes, the addition of preoperative CRT to perioperative chemotherapy does not improve OS compared with perioperative chemotherapy alone in patients with resectable gastric/GEJ adenocarcinoma,” the researchers concluded.