Analysis of prognosis factors in patients with metastatic HER2‑positive gastric/cardioesophageal transition cancer treated in oncological clinics of Moscow

Introduction. Cancer of the stomach and cardio-esophageal transition is one of the key causes of mortality from malignant neoplasms in the world. Despite advances in targeted therapy in the treatment of HER2-positive gastric adenocarcinoma, the prognosis for most patients remains poor. The high degree of heterogeneity of the disease, relapse rates and limited treatment efficacy highlight the need to examine factors influencing therapy outcomes and possibility of their accounting in order to perform a personalized treatment.

Aim. To evaluate the factors influencing progression-free survival and overall survival in patients with metastatic HER2-positive gastric cancer and/or cardio-esophageal transition.

Materials and methods. The study included data from patients with metastatic HER2- positive gastric cancer from 5 oncology hospitals who received 1st-line trastuzumab between 2019 and 2024. Statistical analysis was performed using univariate and multivariate analyses to assess the impact of different clinical characteristics on progression-free survival and overall survival.

Results. The study included 117 patients with metastatic gastric cancer who received trastuzumab in the 1st line of therapy. In univariate analysis of patient characteristics, the presence of bone metastases, age over 65 years, presence of ascites, ECOG status 1–2, degree of G3 differentiation, female sex were prognostically significant for progression-free survival and overall survival. As a result of multivariate analysis, age 65 years and older (p = 0.016), female sex (p = 0.003), presence of poorly differentiated tumors (p = 0.021), the presence of metastases in supraclavicular lymph nodes (p = 0.043) were prognosis factors associated with decreased overall survival. And the presence of secondary foci in bones was an independent prognosis factor associated with decrease in PFS according to results of multifactorial analysis (p = 0.043).

Conclusion. Despite the effectiveness of targeted therapies, factors such as age, sex, functional status and metastasis localization have a decisive impact on the disease prognosis. Analysis of larger sample of patients is needed to definitively confirm the findings.

1. Bray F., Laversanne M., Sung H. et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024;74(3):229–63. DOI: 10.3322/caac.21834

2. Belkin E.V., Tulin P.E., Abu-Khaydar O.B. et al. PET/CT with 68Ga-FAPI and 18F-FDG in the Detection of Metastases in Regional Lymph Nodes in Gastric Cancer. Journal of Oncology: diagnostic radiology and radiotherapy 2025;8(1):29–35. (In Russ.). DOI: 10.37174/2587-7593-2025-8-1-29-353.

3. Abu-Haidar O.B., Gladilina I.A., Kononets P.V., Tryakin A.A. 8th edition AJCC/UICC Staging of Cancers of the Esophagus and Esophagogastric Junction. Journal of Oncology: diagnostic radiology and radiotherapy 2024;7(2):76–85. (In Russ.). DOI: 10.37174/2587-7593-2024-7-2-76-85

4. Fitzmaurice C., Dicker D., Pain A. et al. The Global burden of cancer 2013. JAMA Oncol 2015;1(4):505–27. DOI: 10.1001/jamaoncol.2015.0735

5. Van der Geer P., Hunter T., Lindberg R.A., Receptor proteintyrosine kinases and their signal transduction pathways. Ann Rev Cell Biol 1994;10:251–337. DOI: 10.1146/annurev.cb.10.110194.001343

6. Skórzewska M., Gęca K., Polkowski W.P. A clinical viewpoint on the use of targeted therapy in advanced gastric cancer. Cancers (Basel) 2023;15(22):5490. DOI: 10.3390/cancers1522549

7. Lei Y.-Y., Huang J.-Y., Zhao Q.-R. et al. The clinicopathological parameters and prognostic significance of HER2 expression in gastric cancer patients: a meta-analysis of literature. World J Surg Oncol 2017;15(1):68. DOI: 10.1186/s12957-017-1132-5

8. Bang Y.-J., Van Cutsem E., Feyereislova A. et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010;376(9742):687–97. DOI: 10.1016/S0140-6736(10)61121-X

9. Kim H.W., Kim J.-H., Lim B.J. et al. Sex Disparity in gastric cancer: female sex is a poor prognostic factor for advanced gastric cancer. Ann Surg Oncol 2016;23(13):4344–51. DOI: 10.1245/s10434-016-5448-0

10. Li Q., Li H., Jiang H. et al. Predictive factors of trastuzumab-based chemotherapy in HER2 positive advanced gastric cancer: a single-center prospective observational study. Clin Transl Oncol 2018;20(6):695–702. DOI: 10.1007/s12094-017-1772-5

11. Sun D.S., Jeon E.K., Won H.S. et al., Outcomes in elderly patients treated with a single-agent or combination regimen as first-line chemotherapy for recurrent or metastatic gastric cancer. Gastric Cancer 2015;18(3):644–52. DOI: 10.1007/s10120-014-0405-8

12. Cunningham D., Starling N., Rao S. et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 2008;358(1):36–46. DOI: 10.1056/NEJMoa073149

13. Lee S.S., Lee J.-L., Ryu M.-H. et al. Combination chemotherapy with capecitabine (X) and Cisplatin (P) as first line treatment in advanced gastric cancer: experience of 223 patients with prognostic factor analysis. Jpn J Clin Oncol 2007;37(1):30–7. DOI: 10.1093/jjco/hyl134

14. Kim T.-H., Cho H.D., Choi Y.W. et al. Trastuzumab-based palliative chemotherapy for HER2-positive gastric cancer: a singlecenter real-world data. BMC Cancer 2021;21(1):325. DOI: 10.1186/s12885-021-08058-2

15. Choi J.-H., Choi Y.W., Kang S.Y. et al., Combination versus singleagent as palliative chemotherapy for gastric cancer. BMC Cancer 2020;20(1):167. DOI: 10.1186/s12885-020-6666-1

16. Arias-Martinez A., Martínez de Castro E., Gallego J. et al. Is there a preferred platinum and fluoropyrimidine regimen for advanced HER2-negative esophagogastric adenocarcinoma? Insights from 1293 patients in AGAMENON-SEOM registry. Clin Transl Oncol 2024;26(7):1674–86. DOI: 10.1007/s12094-024-03388-6

17. Soularue É., Cohen R., Tournigand C. et al. Efficacy and safety of trastuzumab in combination with oxaliplatin and fluorouracil-based chemotherapy for patients with HER2-positive metastatic gastric and gastro-oesophageal junction adenocarcinoma patients: a retrospective study. Bull Cancer 2015;102(4):324–31. DOI: 10.1016/j.bulcan.2014.08.001