Esophagogastric Cancers: Integrating Immunotherapy Therapy Into Current Practice

Abstract

Immunotherapy (IO) agents have led to significant improvements in patient outcomes across many tumor types. There have been great efforts to introduce immune checkpoint inhibitors into the treatment paradigm of esophagogastric cancers as well. A number of randomized phase III trials, which will be reviewed here, established the role of these agents in both early-stage and advanced-stage disease. Adjuvant nivolumab is US Food and Drug Administration–approved after neoadjuvant chemoradiation and resection of esophageal and gastroesophageal junction cancers on the basis of the phase III CheckMate 577 trial. In the advanced setting, patients with programmed death receptor ligand-1–positive tumors should be recommended IO in combination with chemotherapy in the first-line setting on the basis of the results from KEYNOTE 590, CheckMate 649, and CheckMate 648. Across trials, chemotherapy continues to play a critical role in the first-line setting and should be offered to all patients who are eligible for systemic therapy, including those with biomarker select tumors. In the later lines of treatment, IO has modest activity, and prior studies have grown largely irrelevant because of the enrollment of IO-naive patients. Similar to other disease types, patients with microsatellite unstable (microsatellite instability high) tumors represent a unique cohort that is more sensitive to IO. However, there are no randomized studies evaluating how best to apply IO in early or advanced stages specifically for the treatment of patients with microsatellite instability high upper GI tumors. Questions remain how to best select patients who benefit from IO treatments, how to augment IO activity in programmed death receptor ligand-1–negative tumors, and how to incorporate IO in late-line settings or for recurrent disease that has been treated with IO-containing regimens during early stages.

Toxicity profile of combined immune checkpoint inhibitors and thoracic radiotherapy in esophageal cancer: A meta-analysis and systematic review

“…While the potential capability of this combination modality has fallen under the spot-light, the frequency and spectrum of treatment-related AEs (trAEs) during the procedure are yet to be detailed in esophageal cancer, with most toxicity data coming from individual clinical trial reports. Given the expected increased application of this combination therapy to esophageal cancer patients in the immediate future ( 16 ), treating physicians must comprehensively understand the spectrum and severity of the toxicities associated with these therapies, in turn shedding light on their clinical application and on the design of prospective trials. Hence, we conducted a systematic review focused on prospective clinical trials evaluating the AEs of the combination of TRT with ICIs in the field of esophageal cancer.…”

Prognostic model construction and validation of esophageal cancer cellular senescence-related genes and correlation with immune infiltration

“…Immunotherapy has made brilliant achievements in the field of advanced EC treatment, rewriting the treatment paradigm of EC ( 47 , 48 ). KEYNOTE-590 is the first global multicenter phase III clinical trial exploring the efficacy of immune combination chemotherapy in advanced EC ( 49 ).…”

Influences of intratumoral heterogeneity on assessment of tumor microenvironment in esophageal squamous cell carcinoma

“…33,38 PD-L1 expression has been evaluated in clinical trials based on two different scoring systems: TPS and CPS. 39,40 Given that TPS + tumors can be detected with CPS scoring, applying CPS analysis across all upper gastrointestinal tumors would presumably be reasonable. 39 In our analysis, the intratumoral heterogeneity of PD-L1 increased when evaluated with TPS.…”