No Survival Gain With Preoperative CRT Plus Perioperative Chemo for Gastric Cancer

Adding preoperative chemoradiotherapy to perioperative chemotherapy failed to boost survival, versus perioperative chemotherapy alone, in resectable gastric and gastroesophageal junction (GEJ) adenocarcinoma, according to TOPGEAR data.

At a median follow-up of 67 months in the phase III trial, there were no significant differences between groups in terms of overall survival (OS) or progression-free survival (PFS), reported Trevor Leong, MD, of the Peter MacCallum Cancer Centre, University of Melbourne, in Australia.

Median OS was 46.4 months in the preoperative chemoradiotherapy/perioperative chemotherapy (preoperative CRT) group versus 49.4 months in the perioperative chemotherapy alone (perioperative CT) group (HR for death 1.05, 95% CI 0.83-1.31, P=0.70), with 3-year OS rates of 55.1% and 57.7%, respectively, and 5-year OS rates of 44.4% and 45.7%, respectively, he said in a presentation at the European Society for Medical Oncology (ESMO) annual congress in Barcelona.

The OS analysis failed to identify any pre-specified subgroups that saw a benefit with the addition of preoperative CRT, Leong noted. TOPGEAR results were published simultaneously in the New England Journal of Medicine.

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), with 3-year PFS rates of 46.5% and 47.7%, respectively, and 5-year rates of 39.7% and 40.1%, respectively.

However, “the addition of preoperative chemoradiation improved pathological outcomes, with a doubling of the pathological complete response rate, and increased tumor downstaging,” Leong said.

He reported that 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. In addition, more tumors in the preoperative CRT group than in the perioperative CT group were downstaged to pathological stage T1 or T2 (32% vs 25%).

ESMO invited discussant Tania Fleitas Kanonnikoff, MD, PhD, of the Hospital Clínico Universitario de Valencia in Spain, who said that while the use of preoperative CRT had no impact on survival, it 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.”

Leong explained that while the current standard of care (SoC) for resectable gastric cancer in Western countries is perioperative CT — based on results from the MAGIC and FLOT4 trials — preoperative therapy has several advantages, including tumor downstaging and a better side effect profile than postoperative therapy. In addition, he pointed out preoperative CRT is the SoC for some patients with esophageal cancer.

TOPGEAR was an international trial conducted at sites in Australasia, Canada, and Europe that randomized 574 patients with resectable adenocarcinoma of the stomach or GEJ to the preoperative CRT and perioperative CT groups.

Patients had a mean age of about 60 and 73% were male. About 35% of tumors were located in the GEJ, while 88% were clinical stage T3/4, and about 60% were node positive.

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.

Regarding surgical outcomes, Leong reported that preoperative CRT did not affect rates of curative resection, as 92% in the preoperative CRT group and 88% in the perioperative CT group had a margin-free resection.

Treatment-related adverse events were similar between the two groups. The overall rates of GI toxicity were 28.2% in the preoperative CRT arm and 25.1% in the perioperative CT arm, while the rates of hematologic toxicity were 45.9% and 41.5%, respectively.

Overall grade ≥3 surgical complications were also comparable between the groups — 17.8% in the preoperative CRT group versus 15.6% in the perioperative CT group.

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