Background and aims: In gastric cancer (GC), HER2 was the first biomarker for guided therapy registered for clinical use. Considering the recent approvals of immune check-point blockade (ICB) in gastro-oesophageal cancers, testing for mismatch repair deficiency (dMMR), Epstein-Barr virus (EBV) and PD-L1 combined positive score (CPS) is becoming increasingly important. Here we describe a real-world cohort on biomarker assessment in GC patients.
Methods: Patients diagnosed with GC between 2017 and 2021 were included. Biomarker results were retrieved from electronic patient files. PD-L1 CPS was determined retrospectively on dMMR and EBV-positive (EBV+) tumours. Data on genomic sequencing were analysed separately.
Results: Of 363 patients identified, 45% had metastatic disease. In 335 patients (92%) at least one biomarker was tested. The prevalence of HER2+, dMMR and EBV+ tumours was 10% (32 of 319), 7% (20 of 294) and 1% (three of 235), respectively. Of the dMMR and EBV+ tumours, 95% had a PD-L1 CPS ≥ 5. Therapeutic strategy was adjusted in 31 of 55 patients and consisted of anti-HER2 therapies as well as ICB in clinical trials. Genomic alterations were found in 44 of 60 tested patients. TP53 (73%) and PIK3CA (20%) mutations were most common, followed by KRAS mutations (11%) and amplifications (11%).
Conclusions: In this real-world cohort, testing for HER2, dMMR and EBV status affected treatment decisions in 56% of the patients. Although most dMMR and EBV+ tumours had a PD-L1 CPS ≥ 5, not all patients with a high probability of treatment response are identified. Based on these results, a stepwise diagnostic strategy is proposed.
Keywords: PD-L1 CPS; gastric cancer; immunotherapy; mismatch repair deficiency; predictive biomarkers.
© 2023 John Wiley & Sons Ltd.