Impact of adding ramucirumab to paclitaxel in patients with advanced gastric cancer according to the level of ascites: A multicenter retrospective study

Background: Adding ramucirumab (Ram) to paclitaxel (PTX) improved the overall survival (OS) in patients with advanced gastric cancer (AGC) in the RAINBOW trial, which excluded patients with high levels of ascites. Methods: This retrospective study included patients with AGC who received PTX alone or PTX+Ram as a 2nd-line treatment from Nov. 2013 to Nov. 2016. Selection criteria were ECOG PS of 0–2, refractory or intolerant to fluoropyrimidines, and no prior use of taxane or Ram. The level of ascites was classified as low (no or limited to either the pelvic cavity or upper abdomen) or high (extended from the pelvic cavity to the upper abdomen). An adjusted HR (aHR) for progression-free survival (PFS) and OS was calculated by a multivariate Cox model that contained variables with p < 0.05 in the univariate analysis to reduce imbalance between both treatments. Results: Among 305 patients, 201 (PTX/PTX+Ram, 115/86) and 104 patients (PTX/PTX+Ram, 63/41) were classified into the low and high ascites groups, respectively. There were no significant differences in the baseline characteristics between PTX and PTX+Ram in either group, excepting the proportion of patients with PS of 2 (PTX/PTX+Ram, 18/9% and 24/10% in the low and high groups, respectively) and high ALP levels (PTX/PTX+Ram, 36/23% in the low group). The median PFS in PTX/PTX+Ram was 3.0/5.2 months (m) (HR 0.56, 95%CI 0.42–0.75, p < 0.0001; aHR 0.59, 95%CI 0.44–0.79, p = 0.0004) in the low group and 2.2/3.5 m (HR 0.61, 95%CI 0.40–0.92, p = 0.02; aHR 0.57, 95%CI 0.42–0.77, p = 0.0003) in the high group, and the median OS was 6.9/10.6 m (HR 0.67, 95%CI 0.48–0.93, p = 0.02; aHR 0.69, 95%CI 0.49–0.97, p = 0.03) in the low group and 4.8/6.2 m (HR 0.57, 95%CI 0.37–0.88, p = 0.01; aHR 0.64, 95%CI 0.40–0.99, p = 0.046) in the high group. The incidence of febrile neutropenia was not different between PTX (3%) and PTX+Ram (3%) in the low group but was higher in PTX+Ram (12%) than in PTX (3%) in the high group. Conclusions: Our study suggests that adding Ram to PTX may prolong survival in patients with AGC, regardless of the level of ascites. However, there is a risk of febrile neutropenia when administering PTX+Ram to patients with a high level of ascites. Legal entity responsible for the study: Shigenori Kadowaki. Funding: Has not received any funding. Disclosure: T. Masuishi, N. Boku, K. Muro: Honoraria: Lilly S. Kadowaki: Research funding: Lilly. All other authors have declared no conflicts of interest.