Outcomes relative to paclitaxel dose-intensity when administered with ramucirumab in gastric and gastroesophageal junction (GEJ) adenocarcinoma.

Abstract

e16539 Background: Combination paclitaxel (PTX) and ramucirumab (RAM) is standard second-line treatment for gastric and GEJ cancers. Peripheral neuropathy (PN) is considered a potential obstacle to administering a maximal dose of PTX, potentially limiting efficacy. We sought to determine the dose-intensity and outcomes for patients receiving this treatment. Methods: A retrospective analysis of gastric and GEJ cancer patients treated at Princess Margaret Cancer Centre (2012-2017) was performed identifying all patients who received PTX and RAM during their treatment course. The primary objective was to determine the dose-intensity of PTX administration. Secondary objectives included identification of the reason for dose-reduction (DR), and comparing progression-free survival (PFS) and overall survival (OS) in relation to PTX DR. Results: 45 patients were included in the study. Mean age was 57.2y, 34 (76%) were male, 7 (16%) were Asian, 5 (11%) patients were her2 positive. 42 (93%) patients received first-line treatment containing a potential neuro-toxic agent (cisplatin, oxaliplatin, docetaxel or paclitaxel). 22 (49%) subjects required PTX DR. The median number of cycles administered for subjects not requiring a DR and those with dose-reduced PTX was 3 v 6 (p < 0.001) respectively, with the median number of PTX doses administered 8 v 15 (p0.0022). The mean dose-intensity was 100 v 83% (p < 0.001). PN was the reason for DR in 32% (n = 7) of subjects, whilst neutropenia was 41% (n = 9). The reason for treatment cessation was disease progression in 91% of subjects, irrespective of whether they required a DR or not. Median PFS was 2.8m (95% CI 2.1-4.8) (100% dose PTX) and 5.5m (95% CI 4.8-8.6) in those requiring a DR (p0.0006). Median OS, measured from the initial diagnosis of incurable/metastatic disease was 16.4m (95% CI 13.7-22.9) and 18.5m (95% CI 14.9-47.5) respectively (p0.0953). Conclusions: Approximately half of the patients required a PTX DR, of whom a clinically significant 32% were DR due to PN, slightly less than those DR due to neutropenia. PFS was longer in those requiring a DR, which may reflect that those on treatment longer are more likely to experience toxicity and require a subsequent DR. PTX DR did not significantly affect OS, thus whilst PTX toxicity remains a clinical concern we did not identify that a DR resulted in an appreciable difference in treatment efficacy.