PT  - JOURNAL ARTICLE
AU  - Paschold, Lisa
AU  - Stein, Alexander
AU  - Thiele, Benjamin
AU  - Tintelnot, Joseph
AU  - Henkes, Svenja-Sibylla
AU  - Coith, Cornelia
AU  - Schultheiß, Christoph
AU  - Pantel, Klaus
AU  - Riethdorf, Sabine
AU  - Binder, Mascha
TI  - First-line treatment of unresectable or metastatic HER2 positive esophagogastric adenocarcinoma: liquid biomarker analysis of the phase 2 INTEGA trial
AID  - 10.1136/jitc-2023-006678
DP  - 2023 Jun 01
TA  - Journal for ImmunoTherapy of Cancer
PG  - e006678
VI  - 11
IP  - 6
4099  - http://jitc.bmj.com/content/11/6/e006678.short
4100  - http://jitc.bmj.com/content/11/6/e006678.full
SO  - J Immunother Cancer2023 Jun 01; 11
AB  - Background The addition of nivolumab to trastuzumab and chemotherapy in first-line unresectable or metastatic HER2 positive esophagogastric adenocarcinoma (HER2+ EGA) results in long progression-free and overall survival as shown by the INTEGA (ipilimumab or FOLFOX in combination with nivolumab and trastuzumab in HER2 positive esophagogastric adenocarcinoma) trial. This trial suggested that the chemotherapy backbone is needed in an unselected HER2+ patient population. Yet, it remains an open question if there are specific patient subsets that may benefit from an enhanced immunotherapeutic but chemotherapy-free approach.Methods We analyzed blood T cell repertoire metrics determined by next-generation sequencing, circulating tumor cell (CTC) counts detected by CellSearch and their expression of HER2 and PD-L1 as potential liquid biomarkers predicting outcomes on ipilimumab versus FOLFOX (folinic acid, FOL, fluorouracil, F, oxaliplatin, OX) chemotherapy added to a backbone of trastuzumab and nivolumab in patients with HER2+ EGA in the INTEGA trial population.Results Patients with two out of three baseline-determined liquid biomarkers—high T cell repertoire richness, absence of CTCs or HER2-expression on CTCs—made up approximately 44% of HER2+ EGA cases and did not show compromise in efficacy if treated with a chemotherapy-free regimen. Long-term responders showing a progression-free survival of >12 months were enriched in this biomarker triad, especially if treated on the chemotherapy-free arm.Conclusion Prospective validation of this liquid biomarker triad is needed to molecularly define HER2+ EGA patient subsets with different needs in the first-line systemic treatment setting.Data are available in a public, open access repository. The datasets generated for this study can be found in the European Nucleotide Archive (ENA) under accession number ID: PRJEB55475.