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Background: Ramucirumab (RAM) is a fully human IgG1 monoclonal vascular endothelial growth factor receptor-2 (VEGFR-2) antibody. We previously reported the efficacy and safety of RAM plus irinotecan (IRI) combination therapy in the second-line treatment for advanced gastric cancer (AGC). This is an updated analysis of the HGCSG1603 trial.Methods: This non-randomized, single-arm, phase 2 trial was carried out at 22 institutes in Japan. AGC patients with refractory or intolerance to primary chemotherapy were eligible. RAM 8mg/kg plus IRI 150 mg/m2 combination therapy administered every two weeks was continued until progression or emergence of adverse events requiring discontinuation. The primary endpoint was progression-free survival (PFS) rate at six months, the target was set as 16% with an expected threshold of 39%. A total of 35 cases were planned for registration. The secondary endpoints were overall survival (OS), PFS, response rate (RR), safety, and dose intensity (DI).Results: Between Jan 2018 and Sept 2019, 35 patients were enrolled. Median age was 70 (range, 47-80); female/male were 10/25; ECOG PS 0/1, 22/13, respectively. PFS rate at six months was 26.5% (95%C.I., 13.2-41.8%, p¼0.1353). Median PFS and OS were 4.2 (95%C.I., 2.5-5.4 months) and 9.6 months (95%C.I., 6.4-16.6 months). In the analysis of patients aged 70 years or older and younger than 70 years, PFS was 2.8 and 4.2 months, and OS was 5.1 and 15.6 months, respectively. The efficacy of this therapy was shown even in the elderly. The median relative dose intensity was 96.6% (range 47.3-150) for RAM and 77.3% (range 32.5-100) for IRI, respectively. RR was 26% and disease control rate was 85%. Grade 3 or higher adverse events that occurred in more than 5% of patients were neutropenia (51%), leucopenia (43%), anemia (20%), anorexia (14%), febrile neutropenia (11%), diarrhea (9%), hypertension (9%), proteinuria (9%), hypokalemia (9%), hypoalbuminemia (9%), thrombocytopenia (6%), and hyponatremia (6%). No deaths or new safety signals with a causal relation to study treatment were observed.Conclusions: Although the primary endpoint was not achieved statistically, the results are clinically encouraging, especially taking into account that more elderly patients enrolled in this trial. The combination therapy of RAM plus IRI has anti-cancer activity and a manageable safety profile. This therapy may be considered as one option in second-line treatment for patients with AGC.Clinical trial identification: This trial was registered with Japan Registry of Clinical Trials, number jRCTs011180029.Legal entity responsible for the study: The authors.

BackgroundThere is neither consensus on firstline chemotherapy for advanced gastric cancer (AGC) nor new drugs or schemes approved in recent years.PurposeTo evaluate the evolution in use and effectiveness of firstline polychemotherapy regimens over an 8 year period in AGC.Material and methodsPatients with AGC treated with polychemotherapy were included from 2009 to 2016 in the AGAMENON multicentre observational study to assess prognostic factors and patterns of care. Firstline regimens were grouped into docetaxel or epirubicin containing triplets, fluorouracil plus oxaliplatin, cisplatin or irinotecan doublets, capecitabine plus oxaliplatin or cisplatin doublets and others. According to the year of their first chemotherapy cycle, patients were assigned to one of two groups: the first, from 2009 to 2012, or the second, from 2013 to 2016. Clinical data were obtained from the medical records, after approval by the ethics committee, and introduced into the website of the study. The main clinical variables, progression free survival (PFS) and overall survival (OS), were analysed using the Kaplan–Meier method and compared with a log rank test.ResultsThe AGAMENON registry contains data from 1252 patients, 448 of whom were treated with a chemotherapy regimen in the first period and 804 in the second. Clinical baseline characteristics of the two populations, 2009–2012 versus 2013–2016, were similar: ECOG performance status ≥2, 16.5 versus 13.7%; men, 66.2% versus 71.7%; median age 65.0 versus 64.0 years; Lauren classification, intestinal 52.2 versus 49.1%; HER-2 overexpression, 18.7 versus 17.9%; and ≥3 metastatic sites, 38.4 versus 31.2%, respectively.The use of fluorouracil and oxaliplatin increased from 5.4% to 18.3% while capecitabine–cisplatin (22.1 to 12.3) and docetaxel triplets (13.0 to 6.0) use decreased, comparing the first and second periods. Median OS were 10.3 (95% CI 9–11) and 10.8 (10–12) months for patients in the 2009–2012 and 2013–2016 groups, respectively. Median PFS were 6.5 (95% CI 6–7) and 6.7 months (95% CI 6–7) in 2009–2012 and 2013–2016, respectively. These results show that OS and PFS were similar in both groups (log rank p=0.684 and 0.714).ConclusionAlthough there were changes in chemotherapy regimens usage, survival remained almost constant over time, pointing to the need for new treatment strategies in AGC.References and/or acknowledgementsThe investigators of the AGAMENON study.No conflict of interest