A multi-center phase II study of chemotherapy (SOX) plus tislelizumab as first-line therapy for gastric cancer with liver metastasis.

Abstract

e16047 Background: Grim prognosis and medical scarcities of gastric cancer (GC) with liver metastasis (LM) presents the significant challenge. Chemotherapy plus programmed cell death inhibitors provided promising opportunities to solve such problems and the dedicated trail is warranted. Methods: In this prospective, single-arm phase 2 trail, untreated synchronous GC-LM are eligible and receive SOX plus Tisleizumab (200mg, Q3W) for 8 cycles, maintenance therapy is S-1 within 1 year plus Tisleizumab within 2 years, or until disease progression. The primary endpoint was objective response rate (ORR), secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). This exploratory study hypothesized chemotherapy plus tislelizumab would increase ORR from 25% to 56%, with one-sided α of 0.05, statistical power of 0.8, considering 10% dropout, 33 patients are required. Results: 34 patients were enrolled and 4 patients were excluded from efficacy analysis (3 withdrawal of consent, 1 loss to follow-up). Median follow-up was 24.00m (14.18-33.82, 95%CI). ORR is 73.33% (22/30) and DCR is 86.67% (26/30). Median PFS and OS is 21.00m (14.13-27.87) and 24.00m (14.18-33.82). Mean maximal tumor volume regression of GC is 36.17% and the time to reach maximal tumor regression is 3.5m, correspondingly, 46.67% and 3.87m are observed in LM. 33.33% (10/30) patients received conversion surgery (CS) and TRG0 ratio is 16.67% (5/30). CS has significantly better median OS (P = 0.004) and median PFS/DFS (P = 0.005). Conclusions: Chemotherapy (SOX) plus Tisleizumab as first line treatment of GC-LM demonstrated clinically meaningful benefits in both treatment response and prolonged survival. Particularly, increased CS rate provided additional survival benefits. Clinical trial information: NCT05325528 . N MedianOS (95% CI) P-value MedianPFS (95% CI) P-value All patients 30 Age ≥65 18 28.00 (NR-NR) 0.129 21 (NR-NR) 0.273 ＜65 12 20.00 (NR-NR) 16.00 (NR-NR) Sex Female 3 28.00 (10.17-45.83) 0.526 17.00 (NR-NR) 0.525 Male 27 24.00 (NR-NR) 21.00 (1.37-40.63) N stage N1-2 18 24.00 (NR-NR) 0.710 17.00 (NR-34.31) 0.736 N3a&b 12 28.00 (NR-NR) 21.00 (NR-NR) Gastric tumor diameter<5cm 14 32.48 (NR-NR) 0.068 NR 0.012 diameter≥5cm 16 12.00 (NR-25.28) 4 (NR-18.00) Liver metastasis Unilobar 13 NR (NR-NR) 0.045 NR 0.112 Multilobar 17 20.00 (4.65-35.35) 16.00 (.446-31.55) Tumor number <5 15 20.00 (4.461-35.54) 0.082 NR 0.188 Tumor number ≥5 15 NR (NR-NR) 17.00 (.83-33.17) Maximal tumor diameter<5cm 17 NR (NR-NR) 0.006 27.00 (NR-NR) 0.014 Maximal tumordiameter≥5cm 13 20.00 (3.10-36.89) 16 (NR-34.79) PD-L Negative 13 12.00 (3.39-26.26) 0.407 18.28 (0.00-36.15) 0.654 ≥1 17 28.00 (12.89-43.11) 23.00 (NR-NR) Conversion surgery Yes 10 NR 0.004 NR 0.005 No 20 20.00 (1.19-41.81) 16.00 (0.00-38.99) Recist PR+CR 22 28.00 (NR-NR) 0.001 NR (NR-NR) 0.000 SD+PD 8 5.00 (2.44-7.56) 1.13 (NR)