A PERFECT Biomarker-focused Study of Neoadjuvant IO for Esophagogastric Cancer

Abstract

To evaluate feasibility and efficacy, checkpoint inhibitor atezolizumab was added to neoadjuvant chemoradiotherapy prior to surgery for esophagogastric adenocarcinoma. The approach was deemed feasible, and while it did not demonstrate better clinical outcome to propensity-matched patients, biomarker investigation demonstrated that high inflammation in the sample at baseline predicted therapeutic benefit.See related article by van den Ende et al., p. 3351.

Figure 1:

The work by van den Ende and colleagues (1) identified that patients responding to anti-PD-L1 antibody (atezolizumab) had highly inflamed baseline tumors at diagnosis, as measured by upregulation of various checkpoints, increased CD8+ cells, and upregulated IFN-gamma signature. Non-responding tumors displayed either persistently no/low cytotoxic lymphocytes (CTLs) before or during therapy or CTLs within the tumor bed, but with upregulation of various checkpoints. With this information, an example of a future biomarker-informed study design for locally advanced esophagogastric adenocarcinoma to build on these finding could study novel immunotherapeutic options based on the tumor immune microenvironment profile at baseline and after initiation of therapy as depicted. GEJ, gastroesophageal junction; Tx, treatment; SOC, standard of care; R, randomization; ICIs, immune checkpoint inhibitors; S, surgery. *Including various iterations/combinations of available checkpoint inhibitors (PD-L1, CTLA4, TIGIT, etc).