Subgroup analysis of efficacy and safety of fruquintinib plus paclitaxel versus paclitaxel in gastroesophageal junction adenocarcinoma patients from FRUTIGA: A randomized phase 3 clinical trial in second-line treatment of gastric/gastroesophageal jun

e16012 Background: It has been previously reported that fruquintinib (F)+ paclitaxel (PTX) significantly improved progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) in second-line treatment of patients (pts) with advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma in FRUTIGA study ( Xu R-H, et al, Nature Med. 2024 ). GEJ adenocarcinoma is more aggressive, with a higher incidence of recurrence and worse disease-specific survival, compared with gastric adenocarcinoma ( Nakauchi M, et al, Ann Surg. 2021 ). Here, we present the efficacy and safety of F+PTX versus (vs) placebo (PBO)+PTX in GEJ adenocarcinoma subgroup. Methods: FRUTIGA was a randomized, double-blind, placebo-controlled phase 3 study, in which, eligible pts were randomized to receive F+PTX or PBO+PTX. Exploratory analyses were conducted to evaluate the efficacy and safety between treatment arms based on GEJ adenocarcinoma subgroup. Results: Of the 703 pts enrolled in FRUTIGA, 120 pts had the primary tumor location of GEJ, with 60 pts each in F+PTX arm and PBO+PTX arm.The baseline demographics and disease characteristics were well balanced between treatment arms. In the GEJ subgroup, PFS was significantly improved with F+PTX vs PBO+PTX (median 6.4 months [mo] vs 4.0 mo; HR 0.54 [95% CI 0.35, 0.82], p =0.0031). The ORR and DCR were significantly higher with F+PTX vs PBO+PTX (ORR 45.0% vs 25.0%, p =0.0347; DCR 80.0% vs 61.7%, p =0.0438). Median overall survival (OS) was 13.4 mo with F+PTX and 8.3 mo with PBO+PTX (HR 0.73 [95% CI 0.48, 1.11]; p = 0.1398). These results in GEJ subgroup revealed superior benefit of F+PTX vs PBO+PTX in PFS, ORR and DCR, which were consistent with that in the ITT population of FRUTIGA; and showed more remarkable OS benefit in GEJ subgroup compared with that in the ITT population. The safety profile observed in GEJ subgroup was similar to that in the ITT population ( Xu R-H, et al, Nature Med. 2024 ). Conclusions: F+PTX showed efficacy benefits and tolerable safety profile in GEJ adenocarcinoma pts, which demonstrated favorable clinical value in GEJ adenocarcinoma pts. Clinical trial information: NCT03223376 . F+PTX (N=60) PBO+PTX (N=60) Median PFS (95% CI), month 6.4 (3.9, 8.2) 4.0 (2.7, 4.6) Unstratified HR (95% CI)Unstratified log-rank test p value 0.54 (0.35, 0.82)0.0031 ORR (95% CI), % 45.0 (32.1, 58.4) 25.0 (14.7, 37.9) Odds ratio and 95% CIFisher’s exact test p value 2.46 (1.13, 5.33)0.0347 DCR (95% CI), % 80.0 (67.7, 89.2) 61.7 (48.2, 73.9) Odds ratio and 95% CIFisher’s exact test p value 2.49 (1.1, 5.6)0.0438 Median OS (95% CI), month 13.4 (9.0, 15.5) 8.3 (6.4, 12.6) Unstratified HR (95% CI)Unstratified log-rank test p value 0.73 (0.48, 1.11)0.1398