Tislelizumab improves survival in advanced gastric/gastro-oesophageal junction adenocarcinoma

First-line treatment with tislelizumab plus chemotherapy for advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma yields better overall survival and an acceptable safety profile compared with chemotherapy plus placebo in patients with a programmed death-ligand 1 (PD-L1) tumour area positivity (TAP) score of ≥5 percent, a study has shown.

“These data suggest that tislelizumab plus chemotherapy represents a potential new primary treatment option for patients with advanced gastric or gastro-oesophageal junction adenocarcinoma,” said the researchers led by Professor Miao-Zhen Qiu from the Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, China.

Qiu and colleagues conducted this randomized, double-blind, placebo-controlled, phase III trial at 146 medical centres across Asia, Europe, and North America between 13 December 2018 and 28 February 2023. A total of 1,657 patients aged ≥18 years with advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma were included.

Of the patients, 997 were eligible and randomly assigned to receive either tislelizumab 200 mg (n=501) or placebo (n=496) intravenously every 3 weeks in combination with chemotherapy and stratified by region, PD-L1 expression, presence or absence of peritoneal metastases, and investigator’s choice of chemotherapy (ie, oxaliplatin and capecitabine, or cisplatin and 5-fluorouracil).

Patients with a PD-L1 TAP score of ≥5 percent who received tislelizumab plus chemotherapy enjoyed significantly longer survival than those treated with placebo (median, 17.2 vs 12.6 months; hazard ratio [HR], 0.74, 95 percent confidence interval [CI], 0.59‒0.94; p=0.006). [BMJ 2024;385:e078876]

Similarly, tislelizumab plus chemotherapy significantly improved the overall survival in all randomized patients relative to placebo (median, 15.0 vs 12.9 months; HR, 0.80, 95 percent CI, 0.70‒0.92; p=0.001).

In terms of safety, 268 of 498 (54 percent) patients in the tislelizumab arm experienced grade 3 or worse treatment-related adverse events compared with 246 of 494 (50 percent) patients in the placebo arm.

“Primary treatment of advanced gastric or gastro-oesophageal junction adenocarcinoma with tislelizumab plus chemotherapy provided significant and clinically meaningful overall survival benefit versus placebo plus chemotherapy in patients with a PD-L1 TAP score of ≥5 percent and in all randomized patients,” Qui said.

PD-L1 expression

The significantly better overall survival with the tislelizumab-chemotherapy combination therapy in patients with PD-L1 TAP score of ≥5 percent than in those with a score of <5 percent suggested an improved survival benefit in patients with higher versus lower PD-L1 expression, the researchers said.

“In patients with a PD-L1 TAP score of <5 percent, the HR for overall survival seemed to favour the tislelizumab plus chemotherapy arm over the placebo plus chemotherapy arm (ie, HR <1); a similar trend in the HR for progression-free survival and a numerical increase in objective response rate were also observed,” the researchers said.

“This prespecified exploratory analysis was not powered for hypothesis testing, however, and should be interpreted with caution,” they added.