The AGAMENON-SEOM model for prediction of survival in patients with advanced HER2-positive oesophagogastric adenocarcinoma receiving first-line trastuzumab-based therapy

Author:

Jimenez-Fonseca Paula1,Foy Victoria2,Raby Sophie2,Carmona-Bayonas Alberto3,Macía-Rivas Lola4,Arrazubi Virginia5,Cacho Lavin Diego6,Hernandez San Gil Raquel7,Custodio Ana8,Cano Juana María9,Fernández Montes Ana10,Mirallas Oriol11,Macias Declara Ismael12,Vidal Tocino Rosario13,Visa Laura14,Limón María Luisa15,Pimentel Paola16,Martínez Lago Nieves17ORCID,Sauri Tamara18,Martín Richard Marta19,Mangas Monserrat20,Gil Raga Mireia21,Calvo Aitana22,Reguera Pablo23,Granja Mónica24,Martín Carnicero Alfonso25,Hernández Pérez Carolina26,Cerdá Paula27,Gomez Gonzalez Lucía28,Garcia Navalon Francisco29,Pacheco Barcia Vilma30ORCID,Gutierrez Abad David31,Ruiz Martín Maribel32,Weaver Jamie33,Mansoor Wasat33,Gallego Javier34

Affiliation:

1. Medical Oncology Department, Hospital Universitario Central de Asturias, ISPA, Oviedo, Spain

2. Department of Medical Oncology, Christie Hospital, Manchester, UK

3. Medical Oncology Department, Hospital Universitario Morales Meseguer, Calle Marqués de los Vélez, s/n, Murcia 30007, Spain

4. Pharmacy Department, Hospital Universitario Central de Asturias, Oviedo, Spain

5. Medical Oncology Department, Complejo Hospitalario de Navarra, IdiSNA (Navarra Institute for Health Research), Pamplona, Spain

6. Medical Oncology Department, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain

7. Medical Oncology Department, Hospital Universitario de Canarias, Tenerife, Spain

8. Medical Oncology Department, Hospital Universitario La Paz, CIBERONC CB16/12/00398, Madrid, Spain

9. Medical Oncology Department, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain

10. Medical Oncology Department, Complejo Hospitalario de Orense, Orense, Spain

11. Medical Oncology Department, Hospital Universitario Vall d’Hebron, Vall Hebron Institute of Oncology (VHIO), Barcelona, Spain

12. Medical Oncology Department, Hospital Universitario Parc Tauli, Sabadell, Spain

13. Medical Oncology Department, Complejo Asistencial Universitario de Salamanca-IBSAL, Salamanca, Spain

14. Medical Oncology Department, Hospital Universitario El Mar, Barcelona, Spain

15. Medical Oncology Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain

16. Medical Oncology Department, Hospital General Universitario Santa Lucía, Cartagena, Spain

17. Medical Oncology Department, Complejo Hospitalario Universitario de A Coruña, A Coruña, Spain

18. Medical Oncology Department, Hospital Clinic, IDIBAPS, Barcelona, Spain

19. Medical Oncology Department, Catalan Institute of Oncology, Barcelona, Spain

20. Medical Oncology Department, Hospital Galdakao-Usansolo, Usansolo, Spain

21. Medical Oncology Department, Hospital General Universitario de Valencia, Valencia, Spain

22. Medical Oncology Department, Hospital Universitario Gregorio Marañón, Madrid, Spain

23. Medical Oncology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain

24. Medical Oncology Department, Hospital Universitario Clínico San Carlos, Madrid, Spain

25. Medical Oncology Department, Hospital San Pedro, Logroño, Spain

26. Medical Oncology Department, Hospital Universitario Nuestra Señora de the Candelaria, Santa Cruz de Tenerife, Spain

27. Medical Oncology Department, Hospital Universitario Santa Creu i Sant Pau, Barcelona, Spain

28. Medical Oncology Department, Hospital General Universitario de Alicante, Alicante, Spain

29. Medical Oncology Department, Hospital Universitario Son Llatzer, Mallorca, Spain

30. Medical Oncology Department, Hospital Universitario de Torrejón, Madrid, Spain

31. Medical Oncology Department, Hospital Universitario de Fuenlabrada, Madrid, Spain

32. Medical Oncology Department, Hospital Universitario Rio Carrión de Zamora, Zamora, Spain

33. Department of Medical Oncology, Christie Hospital/University of Manchester, Manchester, UK

34. Medical Oncology Department, Hospital General Universitario of Elche, Elche, Spain

Abstract

Background: Trastuzumab and chemotherapy is the standard first-line treatment in human epidermal growth factor receptor 2 (HER2)-positive advanced gastro-oesophageal cancer. The objective was to develop a predictive model for overall survival (OS) and progression-free survival (PFS) in patients treated with trastuzumab. Methods: Patients with HER2-positive advanced gastro-oesophageal adenocarcinoma (AGA) from the Spanish Society of Medical Oncology (SEOM)-AGAMENON registry and treated first line with trastuzumab and chemotherapy between 2008 and 2021 were included. The model was externally validated in an independent series (The Christie NHS Foundation Trust, Manchester, UK). Results: In all, 737 patients were recruited (AGAMENON-SEOM, n = 654; Manchester, n = 83). Median PFS and OS in the training cohort were 7.76 [95% confidence interval (CI), 7.13–8.25] and 14.0 months (95% CI, 13.0–14.9), respectively. Six covariates were significantly associated with OS: neutrophil-to-lymphocyte ratio, Eastern Cooperative Oncology Group performance status, Lauren subtype, HER2 expression, histological grade and tumour burden. The AGAMENON-HER2 model demonstrated adequate calibration and fair discriminatory ability with a c-index for corrected PFS/OS of 0.606 (95% CI, 0.578–0.636) and 0.623 (95% CI, 0.594–0.655), respectively. In the validation cohort, the model is well calibrated, with a c-index of 0.650 and 0.683 for PFS and OS, respectively. Conclusion: The AGAMENON-HER2 prognostic tool stratifies HER2-positive AGA patients receiving trastuzumab and chemotherapy according to their estimated survival endpoints.

Publisher

SAGE Publications

Subject

Oncology

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