Abstract
Purpose
This study aimed to compare ramucirumab-paclitaxel versus chemotherapy in second-line (2L) advanced gastroesophageal cancer (aGEC) based on HER2 status and analyze prognostic factors.
Methods
The study includes patients from the AGAMENON-SEOM registry with aGEC and known HER2 status who received 2L between 2016 and 2021. The Kaplan–Meier method was used to calculate progression-free survival (PFS) and overall survival (OS) and multivariable Cox regression analysis was done to adjust for confounding variables.
Results
Of the 552 patients who met the selection criteria, 149 (26.9%) had HER2-positive aGEC, 89 were treated with chemotherapy, and 60 with ramucirumab-paclitaxel, and 403 had an HER2-negative aGEC, 259 were treated with chemotherapy, and 144 with ramucirumab-paclitaxel.
In the whole sample, 2L PFS was 3.0 months (95% CI 2.8–3.2), 2L OS, 5.7 months (5.2–6.3), and ramucirumab-paclitaxel versus chemotherapy was associated with increased PFS (HR 0.64, 95% CI 0.53–0.78, p < 0.0001) and OS (HR 0.68, 0.55–0.83, p = 0.0002). Median PFS of ramucirumab- paclitaxel versus chemotherapy was 3.5 vs 2.8 months (HR 0.67, 0.54–0.83, p = 0.0004) in HER2-negative, and 4.7 vs 2.7 months (HR 0.57, 0.40–0.82, p = 0.0031) in HER2-positive aGEC, respectively. Median OS for ramucirumab-paclitaxel versus chemotherapy was 6.6 vs 5 months (HR 0.67, 0.53–0.85, p = 0.0007) in HER2-negative, and 7.4 vs 5.6 months (HR 0.70, 0.53–1.04, p = 0.083) in HER2-positive aGEC, respectively. ECOG-PS, tumor burden, Lauren subtype, and neutrophil–lymphocyte ratio were prognostic factors.
Conclusions
In patients with an aGEC from the AGAMENON-SEOM registry, 2L treatment with ramucirumab-paclitaxel was superior to chemotherapy in PFS, OS and response rate, independent of HER2 status.
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Data availability
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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. Priscilla Chase Duran for editing the manuscript. 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
AGAMENON-SEOM registry has received previous financial support from BMS and Servier with other investigational purposes, and from Lilly for this analysis.
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SV, JG, ACB and PJF, developed the project, analyzed the data, and drafted the manuscript. 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.
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The authors declare no competing interests.
Conflict of interest
JG declares he has received honoraria for advisory consulting and speaking role from Lilly, Servier and BMS. PJF declares she has received honoraria for advisory consulting and speaking from Lilly, MSD and BMS. VA declares she has received honoraria for advisory consulting and speaking role from Lilly, MSD and BMS. AFM declares she has received honoraria for advisory consulting and speaking role from Lilly, Servier, Pierre Fabre, Merck, MSD and BMS. RVT declares she has received honoraria for advisory consulting and speaking from Amgen, Merck, Sanofi, Servier, Bristol-MS, Bayer and Roche and has received support for educational, scientific activities and travel from Amgen, Roche, Lilly, Sanofi, Bristol-MS, Pierre-Fabre and Servier. 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.AGAMENON-C.I.EST:30/14, 26 November 2014).
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Valcarcel, S., Gallego, J., Jimenez-Fonseca, P. et al. Does HER2 status influence in the benefit of ramucirumab and paclitaxel as second line treatment of advanced gastro-esophageal adenocarcinoma? Data from the AGAMENON-SEOM registry. J Cancer Res Clin Oncol 149, 4077–4089 (2023). https://doi.org/10.1007/s00432-022-04294-6
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DOI: https://doi.org/10.1007/s00432-022-04294-6