Session X: Esophageal and Gastric Cancers
The study authors conclude that the combination of pembrolizumab, trastuzumab, and chemotherapy provides a substantial, statistically significant improvement in ORR compared with placebo, trastuzumab, and chemotherapy as 1st-line therapy for HER2-positive, metastatic G/GEJ cancer. They further conclude that along with the durability of responses and the manageable safety profile, their initial data support pembrolizumab plus trastuzumab and chemotherapy as a possible new treatment option for HER2-positive, metastatic G/ GEJ cancer.
The study authors conclude that 2nd-line tislelizumab demonstrated statistically significant and clinically meaningful improvement with a tolerable safety profile in overall survival versus chemotherapy in patients with advanced or metastatic ESCC. Efficacy and safety results from the EU/NA subgroup were consistent with the overall population.
The study authors report results with tiragolumab, a human monoclonal antibody that binds TIGIT- (T-cell Immunoreceptor with Ig and ITIM domains) a novel inhibitory immune checkpoint present on activated T cells and NK cells in multiple cancers - to prevent its interaction with its ligand PVR. According to the study authors, tiragolumab combined with atezolizumab was well-tolerated with an acceptable safety profile. It showed preliminary antitumor activity in heavily pre-treated patients with metastatic esophageal cancers not previously treated with cancer immunotherapy.
The study authors demonstrated with their translational study that several genomic pathways and genera in the gut microbiome were significantly associated with survival time in patients with advanced gastric cancer treated with nivolumab. In addition, they found that the nucleotide metabolism pathway may potentially become a biomarker to predict the prognosis of nivolumab treatment in advanced gastric cancer.
The study authors demonstrated in their post-hoc exploratory analysis clinically meaningful efficacy of T-DXd in HER2+ AGC regardless of the timing of testing for HER2 status or level of plasma ERBB2 amplification in ctDNA. They conclude that plasma ERBB2 copy number or HER2ECD warrants further investigation as a means to enrich a population of T-DXd treatment responders in HER2+ or HER2-low AGC.
The study authors conclude that ALX148 in combination with trastuzumab, ramucirumab, and paclitaxel appears to be well tolerated with no DLTs or MTD reached. The RP2D of ALX148 is 15 mg/kg QW in combination. They further conclude that observed durable responses and initial survival estimates in patients with second-line disease - that had progressed upon prior HER2-directed therapy - warrants further study of this combination in patients with advanced HER2- positive G/GEJ cancer.