GA1 TOPGEAR trial results shows no significant benefit of chemoradiotherapy on long term survival

The GA1 TOPGEAR trial results were presented at the European Society for Medical Oncology Congress (ESMO) in Barcelona, Spain and simultaneously published in the New England Journal of Medicine. 

 TOPGEAR researchers investigated adding concurrent radiotherapy to standard treatment to determine if it would improve pathological complete response rates and ultimately overall survival of these patients with resectable gastric and gastro-esophageal junction adenocarcinoma. The study found that there was no significant benefit of chemoradiotherapy on long term survival which was the main aim of the trial. The survival rate at 5 years was about 45% in both groups. As a result, it is recommended that chemoradiotherapy not become a routine standard of care.

“We now know that with high quality surgery and perioperative chemotherapy, preoperative CRT should not be used in management of patients with resectable gastric cancer,” says Dr. Rebecca Wong, Canadian study chair and Professor, University of Toronto; Director, Education, Radiation Medicine, Princess Margaret Cancer Center, UHN. “The doubling of pathological complete response rates and the absence of incremental moderate to severe toxicities when CRT was used provide important data to guide the future exploration of radiotherapy in the management of gastric cancers.”

These results are a globally significant answer to a long-standing question with implications for clinical practice.  Gastric cancer is the 5th most common cancer and the 4th leading cause of cancer death worldwide.1 In Western countries there is considerable need for new treatment options, where the current standard of care for resectable gastric cancer is perioperative chemotherapy. The results will be practice changing as some centres, particularly in the USA, currently employ preoperative chemoradiotherapy as standard treatment for gastric cancer which is also the treatment for patients with gastro-esophageal junction cancers who comprised one third of the TOPGEAR patient cohort.

This multidisciplinary study involved the collaborative efforts of radiation oncologists, medical oncologists and surgeons worldwide to determine the optimal adjuvant regimen for potentially curable gastric cancer. 

"The completion of this study represents yet another successful collaboration between the Canadian Cancer Trials Group and the Australasian Gastrointestinal Trials Group,” affirms study Senior Investigator Chris O’Callaghan. “For two-decades our groups have been conducting practice changing research and we look forward to continuing this productive partnership to reduce morbidity and mortality and improve the quality of life of cancer patients around the world."

About TOPGEAR

This randomised phase III clinical trial enrolled 574 patients from 70 sites across 15 countries between September 2009 and May 2021. Patients receiving chemoradiotherapy were found to have higher rates of complete response of their tumour at the time of surgery, compared with standard care (17% versus 8%).

The study was led by the Australasian Gastro-Intestinal Trials Group (AGITG) and coordinated by the NHMRC Clinical Trials Centre (NHMRC CTC) at the University of Sydney. It involved the collaborative efforts of the European Organisation for Research and Treatment of Cancer (EORTC), the Trans-Tasman Radiation Oncology Group (TROG) and the Canadian Cancer Trials Group (CCTG). 

Funding was provided by NHMRC grants and Cancer Australia Priority-driven Collaborative Cancer Research Scheme Grant. As well as by AGITG and NHMRC CTC, with regional funding from EORTC and CCTG through Canadian Institutes of Health Research and the Canadian Cancer Society.

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