Isabel Porth, Daniela Hirsch, Yonca Ceribas, Philip Weidner, Wilko Weichert, Thorsten Oliver Götze, Sven Perner, Kim Luley, Christian Moritz Heyer, Carolina de la Torre, Ralf-Dieter Hofheinz, Sylvie Lorenzen, Timo Gaiser
- Background
A subgroup of patients with HER2-positive metastatic gastric and gastroesophageal junction cancers shows long-term response under trastuzumab maintenance monotherapy. Obviously, HER2 status alone is not able to identify these patients. We performed this study to identify potential new prognostic biomarkers for this long-term responding patient group.
Patients and methods
Tumor samples of 19 patients with HER2-positive metastatic gastric and gastroesophageal junction cancer who underwent trastuzumab treatment were retrospectively collected from multiple centers. Patients were divided into long-term responding (n=7) or short-term responding group (n=12) according to progression-free survival (PFS≥12 months vs. PFS<12 months). Next generation sequencing and microarray-based gene expression analysis were performed along with HER2 and PD-L1 immunohistochemistry.
Results
Long-term responding patients had significantly higher PD-L1 combined positive scores (CPS) and CPSBackground
A subgroup of patients with HER2-positive metastatic gastric and gastroesophageal junction cancers shows long-term response under trastuzumab maintenance monotherapy. Obviously, HER2 status alone is not able to identify these patients. We performed this study to identify potential new prognostic biomarkers for this long-term responding patient group.
Patients and methods
Tumor samples of 19 patients with HER2-positive metastatic gastric and gastroesophageal junction cancer who underwent trastuzumab treatment were retrospectively collected from multiple centers. Patients were divided into long-term responding (n=7) or short-term responding group (n=12) according to progression-free survival (PFS≥12 months vs. PFS<12 months). Next generation sequencing and microarray-based gene expression analysis were performed along with HER2 and PD-L1 immunohistochemistry.
Results
Long-term responding patients had significantly higher PD-L1 combined positive scores (CPS) and CPS correlated with longer progression-free survival. PD-L1 positivity (CPS≥1) was further associated with an increased CD4+ memory T-cell score. The ERBB2 copy number as well as the tumor mutational burden could not discriminate between short-term and long-term responding patients. Genetic alterations and co-amplifications in HER2 pathway associated genes such as EGFR, which were connected to trastuzumab resistance, were present in 10% of the patients and equally distributed between the groups.
Conclusion
The study highlights the clinical relevance of PD-L1 testing also in the context of trastuzumab treatment and offers a biological rational by demonstrating elevated CD4+ memory T-cells scores in the PD-L1-positive group.…
