1. Anthracycline-based triplets do not improve the efficacy of platinum-fluoropyrimidine doublets in advanced gastric cancer: AGAMENON study data
I. Macias1, A. Carmona-Bayonas2, M. Ferrer Cardona3, R. Hernández4, A. Custodio5, A. Lacalle6, J.E. Lorenzo Barreto7, I. Echavarria Diaz-Guardamino8, L. Visa9, E. Buxo10, M. Mangas11, A. Azkarate12, A. Diaz13, A. Viudez14, M. Sánchez Cánovas15, A. Ramchandani16, F. Longo17, E. Martínez de Castro18, J. Gallego19, P. Jimenez Fonseca20.
1, 3 Medical Oncology, Hospital de Sabadell Corporacis Parc Tauli, Sabadell, ES, 2, 15 Hematology and Medical Oncology Department, Hospital Universitario (HU) Morales Meseguer, Murcia, ES, 4,7Medical Oncology, HU de Canarias, Santa Cruz, ES, 5Medical Oncology, HU La Paz, Madrid, ES, 6,14Medical Oncology, Complejo Hospitalario de Navarra, Pamplona, ES, 8Medical Oncology, Hospital General Universitario Gregorio Marañon, Madrid, ES, 9Department Medical Oncology, HU del Mar, Barcelona, ES, 10Medical Oncology, HospitaClinic, Barcelona, ES, 11Medical Oncology, Hospital Galdakao-Usansolo, Galdakao-Usansolo, ES, 12Medical Oncology, HU Son Espases, Palma De Mallorca, ES, 13Medical Oncology, HU 12 De Octubre, Madrid, ES, 16Medical Oncology, HU Insular de Gran Canaria, Las Palmas, ES, 17 Medical Oncology, HU Ramón y Cajal, Madrid, ES, 18Medical Oncology, HU Marqués de Valdecilla, Santander, ES, 19Medical Oncology, HU General de Elche, Elche, ES 20Medical Oncology, HU Central de Asturias, Oviedo, ES.
Table 1 Baseline characteristics of patients
Table 2 Cox PH regression for OS in elegible patients
BACKGROUND
RESULTS
Figure 2
Kaplan-Meier OS curve
A total of 1002 patients were included (doublets =653; anthracycline-based triplets, n=349) between January 2008 and december 2016.
Figure 1 illustrates the selection process and table 1 shows the distribution of subject’s baseline characteristics stratified per treatment
Although anthracycline-based triplets are one of the most widely used regimens for the treatment of advanced gastric cancer (AGC) the incremental benefit associated with the inclusion of anthracyclines in therapeutic combinations is unknown.
The aim is to evaluate the efficacy and tolerance of epirubicin triplets vs platinum-fluoropyrimidine doublets in a national AGC registry.
Figure 1
Flowchart of patients in the registry
Table 3 Adverse events recorded after PSM
Response rates (42 vs. 33%, p=0.12) and PFS (HR 0.95, CI 95%, 0.80–1.13, log-rank test, p=0.873) were not significantly higher with epirubicin-based regimens.
The triplets were associated with greater grade 3–4 hematological toxicity, and increased hospitalization due to toxicity by 68%. (Table 3)
The addition of epirubicin is viable, but 23.7% discontinued treatment because of adverse effects or patient decision. (Table 4)
Not meeting eligibility criteria for registry (n=629)*
Unfit for combination chemotherapy (n=495), Monotherapy due to
age (n=69), comorbidities (n=21), poor performance status (n=47)
Did not receive any chemotherapy (n=306)
<6 months from perioperative therapy (n=54)
Declined to participate (n=30)
Missing values (n=202)
Clinical trial without chemotherapy (n=17)
<3 months follow-up (n=171) 
Previous chemotherapy for advanced disease (n=38)
Perioperative therapy within <6 months (n=54) 
Other advanced tumor (n=21)
*Categories were not mutually exclusive
Patients assessed
for eligibility (n=2169)
Analyzed (n=1002)
Not eligible for this analysis (n=538)
Therapy with trastuzumab (n=204)
Docetaxel or irinotecan regimens (n= 279)
No survival data (n=55)
METHODS
Patients with AGC treated with polychemotherapy without trastuzumab at 28 hospitals in Spain between 2008 and 2016 were included.
The effect of anthracycline- based triplets against doublets was evaluated by propensity score matching (PSM) and Cox proportional hazards (PH) regression.
Table 4 Dose of drugs after PSM
CONCLUSIONS
Anthracyclines added to platinum-fluoropy- rimidine doublets did not improve the response rate or survival outcomes in patients with AGC but entailed greater toxicity
The multivariable Cox PH regression failed to detect significantly increased OS in favor of triplets with anthracyclines: HR 0,9 (95% CI, 0,78-1,05), p=0,2 (table 2)
After PSM, the sample contained 325 pairs with similar baseline characteristics.
This method was also unable to reveal an increase in OS: 10.5 (95% CI, 9.7–12.3) vs. 9.9 (95% CI, 9.2–11.4) months, HR 0.91 (CI 95%, 0.76–1.083), and (log-rank test, p = 0.226)
The post-PSM Kaplan Meier OS curves are shown in Figure 2
ACKNOWLEDGEMENTS
The autors wish to acknowledge the patients who participated, and all the study team of AGAMENON
AGAMENON REAL DATABASE Madrid, Spain; 8-12 September; Contact