Adding preoperative chemoradiotherapy to perioperative chemotherapy did not significantly improve overall survival (OS) compared to perioperative chemotherapy alone in patients with resectable gastric and gastroesophageal junction (GEJ) adenocarcinoma, according to data from the TOPGEAR trial presented at the European Society for Medical Oncology (ESMO) annual congress.
TOPGEAR Trial Results
In the phase III trial, with a median follow-up of 67 months, researchers observed no significant differences in OS or progression-free survival (PFS) between the two treatment groups. Median OS was 46.4 months in the preoperative chemoradiotherapy/perioperative chemotherapy group versus 49.4 months in the perioperative chemotherapy alone group (HR for death 1.05, 95% CI 0.83-1.31, P = 0.70). Three-year OS rates were 55.1% and 57.7%, respectively, and 5-year OS rates were 44.4% and 45.7%, respectively. Median PFS was 31.4 months in the preoperative CRT group and 31.8 months in the perioperative CT group (HR 0.98, 95% CI 0.79-1.22, P = 0.86).
Pathological Outcomes
Despite the lack of survival benefit, Trevor Leong, MD, of the Peter MacCallum Cancer Centre, University of Melbourne, Australia, noted that "the addition of preoperative chemoradiation improved pathological outcomes, with a doubling of the pathological complete response rate, and increased tumor downstaging." Pathological complete response rates were 16.8% in the preoperative CRT group versus 8.0% in the perioperative CT group, and major pathological response was 49.5% and 29.3% in the two groups, respectively. Additionally, more tumors in the preoperative CRT group were downstaged to pathological stage T1 or T2 (32% vs 25%).
Expert Commentary
Invited discussant Tania Fleitas Kanonnikoff, MD, PhD, of the Hospital Clínico Universitario de Valencia in Spain, suggested that preoperative CRT could be appropriate for patients who might benefit from better tumor downstaging and pathological response, "especially in those patients where we really need to reduce tumor size before surgery."
Current Standard of Care
Leong explained that while the current standard of care for resectable gastric cancer in Western countries is perioperative CT -- based on results from the MAGIC and FLOT4 trials -- preoperative therapy has potential advantages, including tumor downstaging and a better side effect profile than postoperative therapy. Preoperative CRT is the standard of care for some patients with esophageal cancer.
Trial Details
The TOPGEAR trial was an international study conducted at sites in Australasia, Canada, and Europe, randomizing 574 patients with resectable adenocarcinoma of the stomach or GEJ to the preoperative CRT and perioperative CT groups. Patients in both groups received either epirubicin, cisplatin, and fluorouracil or fluorouracil, leucovorin, oxaliplatin, and docetaxel both before and after surgery. The preoperative CRT group also received 45 Gy in 25 fractions of radiation, plus fluorouracil infusion.
Additional Data
An analysis of 7,665 patients with non-metastatic gastric and GEJ tumors showed that patients undergoing perioperative chemotherapy (PC) had the most prolonged overall survival (OS) (median 86.80 months, 95% CI 73.40-NE), followed by neoadjuvant chemotherapy (NC) (median 64.85 months, 95% CI 56.02–72.57). Patients who received chemoradiotherapy in the neoadjuvant and adjuvant settings had worse median OS than PC and NC (NCR 47.15 months, 95% CI 44.58–52.27 and ACR 52.67 months, 95% CI 42.78–63.93).
