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Efficacy and safety of chemotherapy in young patients with advanced gastroesophageal adenocarcinoma: data from the Spanish AGAMENON-SEOM registry

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Abstract

Background

Gastroesophageal adenocarcinoma in young adults (GCYA) counts for 10–15% of diagnoses. Previous studies have mainly focused on surgical outcomes in patients with resectable tumors; however, systemic therapy for advanced GCYA remains under-evaluated. This study aims to assess the efficacy-related outcomes and safety of first-line chemotherapy (CT) in younger versus older patients with advanced gastroesophageal adenocarcinoma.

Methods

Patients with advanced gastroesophageal adenocarcinoma from the AGAMENON-SEOM registry treated with first-line polychemotherapy between January 2008 and October 2022 were included. We compared clinicopathological features, therapies received, efficacy-related outcomes, and toxicity between individuals aged < and ≥ 45 years.

Results

Out of 3386 patients, 263 (7.8%) were < 45 years. Young patients exhibited a higher proportion of females affected, lower ECOG-PS ≥ 2, fewer comorbidities, and more aggressive disease-related features, such as higher proportion of diffuse subtype, signet-ring cells, plastic linitis, grade 3, peritoneal metastases and metastatic disease at diagnosis. They received more triple-agent combinations and underwent more surgeries in metastatic setting. No significant differences were observed between groups in overall response rate (53.1% vs. 52.3% in < and ≥ 45 years, respectively, p = 0.579), progression-free survival (6.1 vs. 6.83 months, p = 0.158) and overall survival (11.07 vs. 10.81 months, p = 0.82), even after adjusting for potential confounding factors. Grade 3–4 adverse events were comparable in both groups, although toxicity leading to treatment discontinuation was more frequent in older patients.

Conclusions

In the AGAMENON-SEOM registry, younger patients with GCYA exhibited more aggressive clinicopathological features, and despite receiving more aggressive treatments, similar efficacy outcomes and toxicity profiles were achieved compared to their older counterparts.

Miniabstract

In the AGAMENON-SEOM registry, GEAC in < 45 years showed more aggressive clinicopathological features and, although treated with more intense first-line CT regimens, similar efficacy outcomes and toxicity were achieved compared to older patients.

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Acknowledgements

AGAMENON registry is part of the Evaluation of Results and Clinical Practice Section included in the Spanish Society of Medical Oncology (SEOM); we are grateful to them for their logistical support of this project. Natalia Cateriano, Miguel Vaquero, and IRICOM S.A. for supporting the registry website. We are indebted to all patients, as well as to AGAMENON centers and investigators who participated in this research and made it possible.

Funding

None to declare. This is an academic study supported by the authors themselves.

Author information

Author notes

  1. Pablo Pérez-Wert and Ana Custodio have contributed equally to the authorship.

Authors and Affiliations

  1. Medical Oncology Department, Hospital Universitario La Paz, CIBERONC CB16/12/00398, Paseo de La Castellana, 261, 28046, Madrid, Spain

    Pablo Pérez-Wert & Ana Custodio

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

    Paula Jimenez-Fonseca

  3. Hematology and Medical Oncology Department, Hospital Universitario Morales Meseguer, University of Murcia, IMIB, Murcia, Spain

    Alberto Carmona-Bayonas

  4. Medical Oncology Department, Hospital Universitario de Navarra, Pamplona, Spain

    Arturo Lecumberri

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

    Diego Cacho Lavin

  6. Biostatistics Unit, IdiPAZ-Hospital Universitario La Paz, Madrid, Spain

    Itsaso Losantos García

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

    Ana Fernández Montes

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

    Juana María Cano

  9. Medical Oncology Department, Hospital Universitario Virgen del Rocío, Seville, Spain

    María Luisa Limón

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

    Raquel Hernández San Gil

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

    Marc Diez

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

    Rosario Vidal Tocino

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

    Ismael Macías Declara

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

    Laura Visa

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

    Paola Pimentel Cáceres

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

    Mireia Gil Raga

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

    Elia Martínez Moreno

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

    Tamara Sauri

  19. Medical Oncology Department, Catalan Institute of Oncology, L’Hospitalet, Spain

    Marta Martín Richard

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

    Mónica Granja

  21. Medical Oncology Department, Hospital Universitario Santa Creu I Sant Pau, Barcelona, Spain

    Paula Cerdà

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

    Lucía Gómez González

  23. Medical Oncology Department, Hospital Universitario de Zamora, Zamora, Spain

    Antonio Mérida-García

  24. Medical Oncology Department, Hospital Universitario Río Carrión, Palencia, Spain

    Maribel Ruiz Martín

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

    Javier Gallego

Authors
  1. Pablo Pérez-Wert
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  2. Ana Custodio
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  3. Paula Jimenez-Fonseca
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  4. Alberto Carmona-Bayonas
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  5. Arturo Lecumberri
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  6. Diego Cacho Lavin
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  7. Itsaso Losantos García
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  8. Ana Fernández Montes
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  9. Juana María Cano
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  10. María Luisa Limón
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  11. Raquel Hernández San Gil
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  12. Marc Diez
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  13. Rosario Vidal Tocino
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  14. Ismael Macías Declara
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  15. Laura Visa
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  16. Paola Pimentel Cáceres
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  17. Mireia Gil Raga
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  18. Elia Martínez Moreno
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  19. Tamara Sauri
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  20. Marta Martín Richard
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  21. Mónica Granja
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  22. Paula Cerdà
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  23. Lucía Gómez González
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  24. Antonio Mérida-García
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  25. Maribel Ruiz Martín
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  26. Javier Gallego
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Consortia

the AGAMENON-SEOM study group

Contributions

PPW, AC, JG, ACB and PJF developed the project, analyzed the data, and drafted the manuscript. ILG has analyzed the data. The other authors recruited patients and provided clinical information, comments, and improvements to the manuscript. All authors participated in the interpretation and discussion of data, and the critical review of the manuscript.

Corresponding author

Correspondence to Pablo Pérez-Wert.

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Conflicts of interest

AC declares she has received payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, educational events or participation on a data safety monitoring board or advisory board from BMS, MSD, Lilly, Ipsen, Novartis and Esteve. PJF declares she has received payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, educational events or participation on a data safety monitoring board or advisory board from Adacap, BMS, Lilly, MSD, Astellas and Astra Zeneca. ACB declares he has received payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing or educational events from Amgen, Astellas, Bayer, BMS, Eisai, Lilly, MSD, Merck, Novartis, Roche and Servier. AL declares he has received support for attending meetings and/or travel from Roche, Pfizer, Lilly and MSD. AFM declares she has received payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing or educational events from Servier, Amgen, Pierre Fabre, Merck, Eisai, Roche, Lilly and Astra Zeneca. MD declares he has received payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, educational events, attending meeting and/or travel from Lilly and BMS. RVT declares she has received payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, educational events, participation on a data safety monitoring board or advisory board, expert testimony, attending meeting and/or travel from Merck, BMS and Amgen. MGR declares she has received grants or contracts from Lilly, Amgen and Servier and payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, educational events, attending meeting and/or travel from Servier, Lilly, Amgen and Merck. MMR declares she has received payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, educational events or participation on a data safety monitoring board or advisory board from BMS, MSD, Astellas y Astra Zeneca. PC declares she has received payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, educational events or participation on a data safety monitoring board or advisory board, attending meeting and/or travel from BMS, Roche, Lilly, Eisai, Servier and Astra Zeneca. JG declares he has received research funding from Astellas, Astra Zeneca, BMS, Daiichi-Sankio, Lilly, Servier and payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, educational events or participation on a data safety monitoring board or advisory board, attending meeting and/or travel from AAA, Amgen, Bayer, BMS, Eisai, Ipsen, Lilly, Merck, MSD, Novartis, Servier, Pierre-Fabre, Roche and Veracyte. The other authors declare that they have no conflict of interest regarding the scope of this article.

Ethics approval and consent to participate

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent or a substitute for it was obtained from all patients before they were included in the study. Ethics committee Hospital General Universitario Morales Meseguer approved the study (C.P.AGAMENONC.I.EST:30/14, 26 November 2014). Informed consent was obtained from all patients before being included in the study. This work is original and has not been previously presented elsewhere.

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Pérez-Wert, P., Custodio, A., Jimenez-Fonseca, P. et al. Efficacy and safety of chemotherapy in young patients with advanced gastroesophageal adenocarcinoma: data from the Spanish AGAMENON-SEOM registry. Gastric Cancer 27, 131–145 (2024). https://doi.org/10.1007/s10120-023-01443-9

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