P-99 Circulating RNA detection, circulating tumor cells count, and molecular tumor profiling in a cohort of untreated metastatic colorectal cancer: A prospective multicenter ancillary study to the randomized VISNÚ trials

Abstract

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.