Background and Importance Trastuzumab associated with chemotherapy (platinum and fluoropyrimidine) is the standard first-line treatment in HER2-positive advanced oesophagogastric adenocarcinoma (AGA); however, its benefits are heterogeneous.

Aim and Objectives To develop and validate a predictive model for overall survival (OS) and progression-free survival (PFS) in patients with AGA treated with trastuzumab.

Material and Methods Patients from the Spanish Society of Medical Oncology (SEOM)-AGAMENON registry with HER2-positive AGA treated in first-line with chemotherapy and trastuzumab between 2008 and 2021 were selected for this study. An accelerated time-to-event model was developed to predict survival and represented as a nomogram and an online calculator. The nomogram was externally validated in an independent series from The Christie NHS Foundation Trust hospital in Manchester, England.

Results 737 patients were recruited (AGAMENON-SEOM, n= 654; Manchester, n= 83). In the referral cohort the median PFS and OS were 7.76 (95% CI, 7.13-8.25) and 14.0 months (95% CI, 13.0-14.9), respectively. Patients received a median of six cycles of platinum, eight cycles of fluoropyrimidine and trastuzumab for a median of 7.6 months (95% CI, 7.10-8.30).

In the validation cohort, the median PFS and OS were 8.1 (95% CI, 7.1-11.3) and 12.8 months (95% CI, 10.3-20.4), respectively. Patients received chemotherapy for a median of five cycles and trastuzumab for a median of 6.3 months.

Six covariates were significantly associated with OS and were used to construct the nomogram: neutrophil-lymphocyte ratio (time ratio (TR):0.73; 95% CI: 0.63-0.83), ECOG status (TR:0.59; 95% CI 0.48-0.73), Lauren histologic subtype (TR:0.73; 95% CI 0.57-0.94), HER2 expression (TR:0.85; 95% CI 0.73-1), histologic grade (TR:0.87; 95% CI 0.72-1.07), and tumour burden (TR:1.69; 95% CI 1.34-2.13). The AGAMENON-HER2 model demonstrated adequate calibration and fair discriminatory ability with a c-index for PFS and OS of 0.606 (95% CI 0.58-0.64) and 0.623 (95% CI 0.59-0.66), respectively. In the Manchester validation cohort, the model is well calibrated, with a c-index of 0.65 and 0.68 for PFS and OS, respectively.

Conclusion and Relevance HER2-positive AGA patients receiving trastuzumab and chemotherapy can be stratified according to their estimated survival endpoints using the AGAMENON-HER2 prognostic tool. This nomogram could be a valuable tool for making treatment decisions in daily clinical practice.

Conflict of Interest No conflict of interest