Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jul;149(7):4077-4089.
doi: 10.1007/s00432-022-04294-6. Epub 2022 Aug 30.

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

Sena Valcarcel  1 , Javier Gallego  2 , Paula Jimenez-Fonseca  3 , Marc Diez  4 , Eva Martínez de Castro  5 , Raquel Hernandez  6 , Virginia Arrazubi  7 , Ana Custodio  8 , Juana María Cano  9 , Ana Fernández Montes  10 , Ismael Macias  11 , Laura Visa  12 , Aitana Calvo  13 , Rosario Vidal Tocino  14 , Nieves Martínez Lago  15 , María Luisa Limón  16 , Mónica Granja  17 , Mireia Gil  18 , Paola Pimentel  19 , Lola Macia-Rivas  20 , Carolina Hernández Pérez  21 , Montserrat Mangas  22 , Alfonso Martín Carnicero  23 , Paula Cerdà  24 , Lucía Gomez Gonzalez  25 , Francisco Garcia Navalon  26 , Mª Dolores Mediano Rambla  27 , Marta Martin Richard  28 , Alberto Carmona-Bayonas  29
Affiliations

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

Sena Valcarcel et al. J Cancer Res Clin Oncol. 2023 Jul.

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.

Keywords: Gastroesophageal adenocarcinoma; HER2; Prognosis; Ramucirumab; Survival.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

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.

Figures

Fig. 1
Fig. 1
Flowchart of the study. *Categories were not mutually exclusive, **Date when ramucirumab was approved in Spain
Fig. 2
Fig. 2
PFS stratified by treatment in HER2+ (A) and negative (B) aGEC
Fig. 3
Fig. 3
OS stratified by treatment in HER2+ (A) and negative (B) aGEC
Fig. 4
Fig. 4
PFS (A) and OS (B) prognostic models. NLR neutrophils/lymphocytes ratio; ECOG PS Eastern Cooperative Oncology Group Performance status. Chemotherapy regimens are those administered in the first line. For the categorical variable “burden of liver disease” the contrast is between each level and the rest. The neutrophil-to-lymphocyte ratio variable has been modeled by means of a restricted cubic splines, illustrating here the prognostic effect of the increase from 2.2 to 5.1 (25% and 75% percentiles, respectively)
See this image and copyright information in PMC

References

    1. Alvarez-Manceñido F, Jimenez-Fonseca P, Carmona-Bayonas A et al (2021) Is advanced esophageal adenocarcinoma a distinct entity from intestinal subtype gastric cancer? Data from the AGAMENON-SEOM Registry. Gastric Cancer 24:926–936. 10.1007/s10120-021-01169-6 - PubMed
    1. Bang Y-J, van Cutsem E, Feyereislova A et al (2010) 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 376:687–697. 10.1016/S0140-6736(10)61121-X - PubMed
    1. Bartsch R, Wenzel C, Altorjai G et al (2007) Capecitabine and trastuzumab in heavily pretreated metastatic breast cancer. J Clin Oncol 25:3853–3858. 10.1200/JCO.2007.11.9776 - PubMed
    1. Bürkner P-C (2017) brms: an R package for bayesian multilevel models using Stan. J Stat Softw. 10.18637/jss.v080.i01
    1. Carmona-Bayonas A, Jiménez-Fonseca P, Lorenzo MLS et al (2016) On the effect of triplet or doublet chemotherapy in advanced gastric cancer: results from a national cancer registry. J Natl Compr Canc Netw 14:1379–1388. 10.6004/jnccn.2016.0148 - PubMed

Supplementary concepts