Certain Biomarkers Associated With Clinical Benefit From Tislelizumab in Advanced Gastric and Gastroesophageal Junction Adenocarcinoma

Patients with advanced gastroesophageal adenocarcinoma who are also PD-L1 positive, have interferon gamma (IFNγ)-related gene signatures, and have tumor mutational burden (TMB)-high status were associated with gaining clinical benefit when treated with tislelizumab, while those with hyperamplification were associated with worse clinical outcomes.

In 2 recent phase 1/2 trials, while tislelizumab was found to have clinical benefit in advanced gastroesophageal adenocarcinoma, a majority of patients did not respond. The study authors stated that this highlights “the need to understand mechanisms of resistance and identify predictive biomarkers for response.”

The 2 studies enrolled a total of 105 patients with gastroesophageal adenocarcinoma between September 2015 and May 2018 who received monotherapy with tislelizumab. The following features were analyzed for correlation with tislelizumab: PD-L1 expression (Tumor Area Expression [TAP] ≥ 5%), IFNγ -related gene signature, gene expression profile, TMB, and gene hyperamplification. There were 90 patients with evaluable PD-L1 expression, 74 with evaluable genomic profiles, 63 with evaluable TMB status, and 80 with evaluable gene expression profiling including 6-gene IFNγ and T cell inflamed signature (TIS) score.

The most favorable benefit was a combination of PD-L1 TAP ≥ 5% and lack of hyperamplification with an objective response rate of 29.4%, median progression-free survival of 4.1 months and median overall survival of 14.7 months. There was a moderate association between PD-L1 TAP ≥ 5%, IFNγ gene signature, TMB-high, and efficacy. A potential correlation was observed between hyperamplification and worse outcomes with PD-L1 inhibition.

The study authors concluded, “combining PD-L1 positivity and lack of hyperamplification may help identify patients more likely to benefit from PD-1 blockade.”

Source:

Lu Z, Yang S, Luo X, et al. The combination of gene hyperamplification and PD-L1 expression as a biomarker for the clinical belief of tislelizumab in gastric/gastroesophageal junction adenocarcinoma. Gastric Cancer. Published online: July 2, 2022.