Results of a phase II trial of ramucirumab plus irinotecan as second-line treatment for patients with advanced gastric cancer (HGCSG 1603).

Abstract

217 Background: Ramucirumab (RAM) is a fully human IgG1 monoclonal vascular endothelial growth factor receptor-2 (VEGFR-2) antibody. The RAINBOW trial showed RAM plus paclitaxel (PTX) increased overall survival (OS) compared with PTX alone for advanced gastric cancer (AGC) in second-line treatment. WJOG 4007 trial demonstrated equivalent efficacy between irinotecan (IRI) and PTX. We conducted this trial to examine the efficacy and safety of RAM plus IRI combination therapy in the second-line treatment for AGC. 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 8 mg/kg and IRI 150 mg/m2 combination therapy administered every two weeks were continued until progression or emergence of adverse events requiring discontinuation. The primary endpoint was progression-free survival (PFS) rate at six-month, the target was set as 16% with an expected threshold of 39%. A total of 35 cases are planned for registration. The secondary endpoints were OS, PFS, response rate (RR) and safety. This trial was registered with Japan Registry of Clinical Trials, number jRCTs011180029. 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. PFS rate at six months was 26.5% (95%C.I., 13.2-41.8%, p = 0.1353). Median PFS and OS were 4.2 (95%C.I., 2.5-5.4 months) and 9.6 months (95%C.I., 6.5-16.6 months), 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 death and 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 take into account that more elderly patients enrolled in this trial. The combination of RAM plus IRI has anti-cancer activity and manageable safety profile in second-line treatment for patients with AGC. Clinical trial information: jRCTs011180029.

Case report of partial response on second line with Ramucirumab and FOLFIRI in treatment of 74 year old male with metastatic HER2-negative gastric adenocarcinoma

“…Комбинация рамуцирумаба с иринотеканом во 2-й линии лечения при дРЖ, апробированная в Японии [26], не достигла главной цели исследования, оказавшись недостаточно эффективной.…”

Treatment strategy for HER2-negative advanced gastric cancer: salvage-line strategy for advanced gastric cancer

“…The combined therapy with ramucirumab and irinotecan demonstrated acceptable safety profile, with no emergence of new or unexpected adverse effects observed in the trial. According to phase II trial investigating the clinical efficiency of ramucirumab plus irinotecan as second-line treatment, median PFS and OS were 4.2 months (95% CI 2.5-5.4 months) and 9.6 months (95% CI 6.4-16.6 months), respectively [30]. The results are similar to that of RIND-BeRG trial, which is in third-or later-line setting, suggesting the efficacy of this regimen even in salvage-line treatment.…”

Augmenting Experimental Gastric Cancer Activity of Irinotecan through Liposomal Formulation and Antiangiogenic Combination Therapy

“…A previous study demonstrated that the combination of bevacizumab, an anti-VEGF antibody, with irinotecan and 5-FU has significant antitumor activity in metastatic colorectal cancer ( 37 ). Recently, a phase II trial of ramucirumab plus irinotecan has shown encouraging results as second-line therapy in gastric cancer ( 38 ).…”