Avoid common mistakes on your manuscript.
Dear Editor,
We read with great interest the paper by Chen et al. reporting the 2-year update analysis of the ATTRACTION-2 trial [1]. At 2 years of follow-up, nivolumab was confirmed to confer an overall-survival (OS) benefit over placebo in heavily pretreated advanced gastric or gastroesophageal junction (G/GEJ) cancer patients (10.6% vs 3.2%) and this was regardless of the presence of potential predictors such as PD-L1 positivity. Radiologic response, however, seemed to be associated with prolonged survival in the nivolumab arm. Other clinical features were not associated with treatment efficacy as shown in a forest plot provided in the supplementary material. In particular, no interaction with the presence of liver or peritoneal metastasis was demonstrated. However, presence of lymph-node metastasis was not included in the subgroup analysis. Lymph-node metastases have been found to be particularly responsive to immune checkpoint inhibitors (ICIs) [2, 3] and also the three complete responses reported in the ATTRACTION-2 were in patients with predominantly lymph node-based metastatic disease.
We recently reviewed 57 patients with mGC treated in second-line with ICIs [4]. Herein we report that patients with lymph node-only metastatic disease had a significantly longer median overall survival as compared to other metastatic patterns (mOS 20.6 vs 4.8 months, HR 0.28, 95% CI 0.12–0.63, p 0.001, see Figure S1). Progression free survival (PFS) and objective response rate (ORR) were similarly significantly improved in the lymph node-only subgroup (mPFS 11 vs. 2 months, HR 0.43, p 0.01 and ORR 33% vs 11%, p 0.05, respectively). Presence of lymph node-only metastasis was confirmed to be an independent prognostic factor in a multivariate cox-regression analysis including gender, primary tumor location, age, Lauren’s subtype, PD-L1 expression, resection of the primary, number of metastatic sites and ECOG performance status (Fig. S1).
Lymph node-only metastatic disease might represent a biologically and phylogenetically distinct entity with peculiar prognosis and response to treatment [5]. Moreover, it can be hypothesized that the increased density and infiltration of lymphocytes in the lymph-node tissue might favor an enhanced ICI-induced immune response against cancer cells metastasizing to the lymph nodes.
We suggest the inclusion of specific metastatic patterns in future subgroup analyses of ICIs in G/GEJ cancer, and in particular we suggest the assessment of the effect of exclusive or predominant nodal metastatic disease in terms of interaction with immunotherapy efficacy.
References
Chen LT, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Sameshima H, Kang YK, Boku N. A phase 3 study of nivolumab in previously treated advanced gastric or gastroesophageal junction cancer (ATTRACTION-2): 2-year update data. Gastric Cancer. 2020;23(3):510–9. https://doi.org/10.1007/s10120-019-01034-7 Epub 2019 Dec 20 PubMed PMID: 31863227.
Schmid S, Diem S, Li Q, et al. Organ-specific response to nivolumab in patients with non-small cell lung cancer (NSCLC). Cancer Immunol Immunother. 2018;67(12):1825–32. https://doi.org/10.1007/s00262-018-2239-4.
Kashima S, Tanabe H, Tanino M, et al. Lymph node metastasis from gastroesophageal cancer successfully treated by nivolumab: a case report of a young patient. Front Oncol. 2019;9:1375. https://doi.org/10.3389/fonc.2019.01375 Published 2019 Dec 16.
Morelli C et al. (2020) Gastric immune prognostic index (GIPI) in metastatic (m) gastro-oesophageal junction (GOJ)/gastric cancer (GC) patients (pts) treated with PD-1/PD-L1 immune checkpoint inhibitors (ICIs). J Clin Oncol 38(4_suppl):417–417. DOI: 10.1200/JCO.2020.38.4_suppl.417
Mangiola S, Hong MK, Cmero M, et al. Comparing nodal versus bony metastatic spread using tumour phylogenies. Sci Rep. 2016;6:33918. https://doi.org/10.1038/srep33918 Published 2016 Sep 22.
Funding
No funding has to be declared.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
No conflict of interest has to be declared.
Ethical standard
All procedures reported herein were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Formica, V., Morelli, C., Patrikidou, A. et al. Lymph node-only metastatic gastric/gastroesophageal junction cancer and efficacy of immunotherapy. Gastric Cancer 23, 1107–1108 (2020). https://doi.org/10.1007/s10120-020-01084-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10120-020-01084-2