Background It is well established that many gastroesophageal (GE) cancers are immune-sensitive. Programmed death ligand-1 (PD-L1) expression may have a predictive value in GE cancers. PD-L1/PD-1 inhibitors have profoundly influenced the cancer treatment landscape in recent years. Assessing PD-L1 levels before and after treatment may help in making appropriate treatment decisions. The purpose of this systematic review was to assess the clinical evidence and impact of various treatment interventions on the dynamics of PD-L1 expression in GE cancers.
Methods A literature search was performed on Medline, Embase, clinicaltrials.gov, and trialtrove using relevant search terms related to PD-L1 and upper GE cancers (Jan 1996-Sep 2022). Two independent reviewers screened and included full-text English articles, while excluding preclinical studies and case reports.
Results Of the 206 articles screened, 38 publications (21 reviews/meta-analyses; 17 research studies) were identified and critically reviewed. PD-L1 is expressed in approximately 30%-65% of tumors in patients with gastric cancers; expression of PD-L1 is positively correlated to the depth of invasion, metastasis, tumor size, and progression.1 PD-L1 levels were also increased in the peripheral blood of patients with gastric cancers.2 3 Higher PD-L1 expression was seen in GE cancers with microsatellite instability and Epstein-Barr virus positivity.4 5 A positive correlation was noted between FOXP3, MLH1, HLA Class I, CD3+/CD8+ T cells expression and PD-L1 levels.1 6 7 PD-L1 expression has been associated with worse prognosis and shorter survival in GE cancers (hazard ratio range: 1.42–1.74).6 8–13 Enhanced responses to immunotherapy have been observed in patients with greater PD-L1 combined positive score (CPS) in GE cancers.1 4 14–17 The pre- and post-treatment PD-L1 levels in GE cancers have been found to differ, with increased levels observed after targeted therapy, chemotherapy, or radiation, although this finding is inconsistent across studies.15 18 19
Conclusions There is a need for standardization of PD-L1 testing recommendations. PD-L1 expression has been associated with poor prognosis and is routinely evaluated before first-line treatment, but there is limited information on the impact of initiated therapy on post-treatment PD-L1 levels. This review suggests that PD-L1 levels may change in response to chemotherapy or radiation, thereby identifying patients suitable for immunotherapy, upon progression. Evaluating PD-L1 levels before initiating second-line therapy is important to ensure the most effective treatment choices.
Acknowledgements The authors received medical writing support for this abstract from Indumathy Pinnamaneni (Novartis Healthcare Pvt. Ltd., Hyderabad, India).
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