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Multicenter Study
. 2017 Sep 5;117(6):775-782.
doi: 10.1038/bjc.2017.245. Epub 2017 Aug 1.

Lauren subtypes of advanced gastric cancer influence survival and response to chemotherapy: real-world data from the AGAMENON National Cancer Registry

Paula Jiménez Fonseca  1 , Alberto Carmona-Bayonas  2 , Raquel Hernández  3 , Ana Custodio  4 , Juana Maria Cano  5 , Alejandra Lacalle  6 , Isabel Echavarria  7 , Ismael Macias  8 , Monserrat Mangas  9 , Laura Visa  10 , Elvira Buxo  11 , Felipe Álvarez Manceñido  12 , Antonio Viudez  6 , Carles Pericay  8 , Aitor Azkarate  13 , Avinash Ramchandani  14 , Carlos López  15 , Eva Martinez de Castro  15 , Ana Fernández Montes  16 , Federico Longo  17 , Rodrigo Sánchez Bayona  18 , Maria Luisa Limón  19 , Asun Diaz-Serrano  20 , Alfonso Martin Carnicero  21 , David Arias  16 , Paula Cerdà  22 , Fernando Rivera  15 , Jose Maria Vieitez  1 , Manuel Sánchez Cánovas  2 , M Garrido  23 , J Gallego  24
Affiliations
Multicenter Study

Lauren subtypes of advanced gastric cancer influence survival and response to chemotherapy: real-world data from the AGAMENON National Cancer Registry

Paula Jiménez Fonseca et al. Br J Cancer. .

Abstract

Background: The choice of chemotherapy in HER2-negative gastric cancer is based on centre's preferences and adverse effects profile. No schedule is currently accepted as standard, nor are there any factors to predict response, other than HER2 status. We seek to evaluate whether Lauren type influences the efficacy of various chemotherapies and on patient overall survival (OS).

Methods: We have conducted a multicenter study in 31 hospitals. The eligibility criteria include diagnosis of stomach or gastroesophageal junction adenocarcinoma, HER2 negativity, and chemotherapy containing 2-3 drugs. Cox proportional hazards regression adjusted for confounding factors, with tests of 'treatment-by-histology' interaction, was used to estimate treatment effect.

Results: Our registry contains 1303 tumours analysable for OS end points and 730 evaluable for overall response rate (ORR). A decrease in ORR was detected in the presence of a diffuse component: odds ratio 0.719 (95% confidence interval (CI), 0.525-0.987), P=0.039. Anthracycline- or docetaxel-containing schedules increased ORR only in the intestinal type. The diffuse type displayed increased mortality with hazard ratio (HR) of 1.201 (95% CI, 1.054-1.368), P=0.0056. Patients receiving chemotherapy with docetaxel exhibited increased OS limited to the intestinal type: HR 0.65 (95% CI, 0.49-0.87), P=0.024, with no increment in OS for the subset having a diffuse component. With respect to progression-free survival (PFS), a significant interaction was seen in the effect of docetaxel-containing schedules, with better PFS limited to the intestinal type subgroup, in the comparison against any other schedule: HR 0.65 (95% CI, 0.50-0.85), P=0.015, and against anthracycline-based regimens: HR 0.64 (95% CI, 0.46-0.88), P=0.046.

Conclusions: As a conclusion, in this registry, Lauren classification tumour subtypes predicted survival and responded differently to chemotherapy. Future clinical trials should stratify effect estimations based on histology.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of patients in the registry. HER2=human epidermal growth factor receptor 2.
Figure 2
Figure 2
Overall response rate according to chemotherapy regimens and Lauren histological type. Data set: subjects with response-evaluable (at 3 months) and initially measurable disease (n=730). DT=diffuse type; IT=intestinal type; ORR=overall response rate.
Figure 3
Figure 3
Forest plot exhibiting the effect of treatment subgroups (hazard ratio for overall survival) according to Lauren histological type. Data set used: patients without indeterminate tumours (n=1134). Test used: HRs are derived from multivariable Cox proportional hazards regression adjusted for gender, ECOG-PS, albumin, histological grade, neutrophil-to-lymphocyte ratio, stage, ascites, bone metastases, lung metastases, and number of metastatic sites (see Materials and Methods section); the effect of subgroups is based on the interaction between Lauren classification (IT & DT) and chemotherapy. The Holm–Bonferroni method was used for multiple comparisons. HR=hazard ratio; N/n=population/events; OS=overall survival.
Figure 4
Figure 4
Forest plot exhibiting the effect of subgroups del treatment (hazard ratio for progression-free survival) according to Lauren histological type. Data set used: patients without indeterminate tumours (n=1134). Test used: HRs are derived from multivariable Cox proportional hazards regression adjusted for ECOG-PS, albumin, neutrophil-to-lymphocyte ratio, ascites, bone metastases, lung metastases, and number of metastatic sites (see Materials and Methods section); the effect of subgroups is based on the interaction between Lauren classification (IT & DT) and chemotherapy. The Holm–Bonferroni method was used for multiple comparisons. HR=hazard ratio; N/n=population/events; PFS=progression-free survival.
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