Impact of subsequent anti-tumor therapies in patients (pts) with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma receiving fruquintinib (F) plus paclitaxel (PTX) or placebo plus PTX in FRUTIGA study

BackgroundFRUTIGA study showed OS improvement but was not statistically significant in the ITT population who had advanced G/GEJ adenocarcinoma receiving F plus PTX over placebo plus PTX (mOS: 9.67 vs 8.41 mo, HR=0.96, p=0.6064; Xu RH, et al, 2024 ASCO #438780). Here we explored the effect of subsequent anti-tumor therapies on OS in this study.MethodsA post-hoc analysis for the effect of subsequent anti-tumor therapies on OS (randomization to death from any cause) using Kaplan-Meier method was conducted.ResultsA total of 439/703 pts (F+PTX vs placebo + PTX: 185/351 [52.7%] vs 254/352 [72.2%]) received subsequent anti-tumor therapies. There were 33.7% (28.2% vs 39.2%), 16.9% (14.2% vs 19.6%), and 9.1% (7.4% vs 10.8%) of pts received 1, 2 or ≥ 3 subsequent anti-tumor regimens, respectively. Apatinib (23.1% vs 35.2%), irinotecan (20.8% vs 27.8%) and anti PD-1/PD-L1 antibodies (20.8% vs 27.6%) were the most common subsequent regimens; few pts (3.4% vs 5.7%) used anti-HER2/Claudin 18.2 regimens. Detailed results of impact of subsequent anti-tumor therapies on OS are shown in the table below. Table: 1434P F+PTX (N = 351) n (%) PTX (N = 352) n (%) Median OS, mo (F+PTX vs PTX) HR Subsequent treatment 185 (52.7) 254 (72.2) 12.22 vs 9.95 0.91 (0.73, 1.12) Apatinib 81 (23.1) 124 (35.2) 13.01 vs 10.81 0.95 (0.70, 1.30) Irinotecan 73 (20.8) 98 (27.8) 12.22 vs 10.71 0.92 (0.67, 1.27) Anti PD-1/PD-L1 – ICI naïve# 68 (19.4) 86 (24.4) 13.90 vs 13.60 1.12 (0.77, 1.62) Anti PD-1/PD-L1 – ICI pre-treated∗ 5 (1.4) 11 (3.1) 14.52 vs 14.75 0.73 (0.18, 2.94) Anti HER2/Claudin 18.2& 12 (3.4) 20 (5.7) 13.77 vs 16.10 2.09 (0.82, 5.30) ∗Pts who had received prior anti PD-1/PD-L1 antibodies treatment.#Pts who had not received prior anti PD-1/PD-L1 antibodies treatment.&Pts who had not received prior HER2. ConclusionsPts who received 3L standard regimens (apatinib, irinotecan) for the subsequent anti-tumor therapies had the consistent OS improvement as shown in ITT population. Subsequent anti PD-1/PD-L1 therapies for pts who had received previous anti PD-1/PD-L1 antibodies could have no potential impact on OS benefit in FRUTIGA study.Clinical trial identificationNCT03223376.Legal entity responsible for the studyHutchmed Limited.FundingThe National Science and Technology Major Project (project no. 2019ZX09301012), the Science and Technology Commission of Shanghai Municipality (Science, Technology and Innovation Action Plan, project no. 17431900100) and Hutchmed Limited.DisclosureP. Tan, W. Su: Financial Interests, Personal, Full or part-time Employment: Hutchmed Limited. All other authors have declared no conflicts of interest.