687P - Phase II clinical trial of second-line weekly paclitaxel plus trastuzumab for patients with HER2-positive metastatic gastric cancer

Abstract

Background: Combination therapy with fluorouracil, platinum, and trastuzumab (Tmab) has been established as the first-line chemotherapy for HER2-positive gastric cancer, but there is no established therapy in the second-line setting. This study aimed to evaluate the efficacy and safety of weekly paclitaxel plus Tmab as second-line chemotherapy for HER2-positive gastric cancer patients. Methods: Eligible patients were ≥ 20 years old, histologically confirmed gastric adenocarcinoma with HER2-positive (IHC3+ or IHC2+ and FISH (or DISH)-positive), previously treated chemotherapy (not except pretreated-Tmab), ECOG PS of 0, 1 or 2, and adequate organ function. Eligible patients received weekly paclitaxel plus Tmab (paclitaxel: 80 mg/m2 IV on day1, 8, 15, repeated every 4weeks, Tmab: 8mg/kg (1st time) IV on day1, after 2nd time, 6mg/kg IV, repeated every 3weeks). All therapy was administered until disease progression. The primary endpoint was response rate, the secondary endpoint were Progression-free survival (PFS), Overall survival (OS) and Toxicity. Results: Twenty-eight patients were enrolled between 08/2011 and 03/2017. Patients characteristics were; median age, 69.5 years; male, 22(79%); ECOG-PS0/1/2, 5(18%)/17(61%)/6(21%); Tmab pretreated/untreated, 20(71%)/8(29%). The overall response rate was 22% with 6 partial responses, 8 stable diseases, 13 progression and 1 not evaluable yet. Median PFS was 4.6 months (95% CI: 2.2-7.0). Median OS was 9.6 months (95% CI: 2.3-16.9). Grade 3/4 toxicities included neutropenia in 36%, leukopenia in 21%, anemia in 11%, anorexia in 7%, febrile neutropenia in 7%, respectively. Tmab beyond progression (TBP) group (n = 20) did not differ from non-TBP group (n = 8) in PFS and OS (PFS; 5.0:2.8 (months), p = 0.369, OS; 12.4:6.1 (months), p = 0.363, log-rank test). And, in TBP group, therapeutic effect was associated with duration of PFS of 1st line Tmab combined chemotherapy (≥ 6 months (n = 10): < 6 months (n = 10), PFS; 6.4:2.8 (months), p = 0.016, OS; Not reached:6.5 (months), p = 0.002, log-rank test). Conclusions: Weekly paclitaxel plus trastuzumab appeared favorable and well tolerated as second-line chemotherapy for HER2-positive gastric cancer patients in this single arm study. Legal entity responsible for the study: Toyama Prefectural Central Hospital Funding: None Disclosure: All authors have declared no conflicts of interest.