ABSTRACT
The introduction of immunotherapy in the therapeutic algorithm of gastroesophageal cancer is still a debated issue. Recent findings from randomized clinical trials documented the efficacy of adjuvant nivolumab in improving disease free survival (DFS) in resectable esophageal and gastroesophageal junction cancer patients with residual pathologic disease after neoadjuvant chemoradiation (Check- Mate 577). Consistently, the combination of pembrolizumab and doublet chemotherapy with 5-fluorouracil plus cisplatin improved first-line treatment outcomes in metastatic esophageal squamous cancer; moreover the most benefit was observed in tumor expressing PD-L1 combined positive score (CPS) > 10 (Keynote 590). Finally, the addition of nivolumab to first-line oxaliplatin and 5-fluorouracil- based chemotherapy improved overall survival survival, progression free survival and response rate in patients with metastatic adenocarcinoma gastric/gastroesophageal junction cancer with PD-L1 positive score (PD-L1 CPS ≥ 5) (CheckMate 649). Moving forward, the research focused on the identification of predictive biomarkers of response to immunotherapy, to refine the patients’ selection and maximize the treatment benefit. Microsatellite instability has been shown to predict higher response to checkpoint inhibitors as highlighted by subgroup analyses of the pivotal studies. For what concerns microsatellite stable tumors, the expression of PDL1, the positivity for Epstein-Barr virus and a high tumor mutational burden are now regarded as the most promising and reliable predictive markers for immunotherapy as far as now. Therefore, the anti-PD1 agents nivolumab and pembrolizumab proved to confer an improvement in the outcome of gastroesophageal cancer patients but the real magnitude of benefit of immunotherapy in this disease setting is under definition. Biomarker-focused research will allow clinicians to define the optimal therapeutic algorithm in the different patients populations.
The use of patient-reported outcomes in clinical practice for patients receiving active anti-cancer treatment is associated with a significant QoL improvement also in older patients.

IMPACT STATEMENT
Immune-checkpoint inhibitors proved to confer a meaningful benefit in the setting of gastric/gastroesophageal junction cancer, nevertheless a refinement of patients selection according to predictive biomarkers could maximize the treatment benefit.