1466P - Efficacy and safety of perioperative chemotherapy combined with tislelizumab and trastuzumab for HER2-positive resectable gastric/gastroesophageal junction cancer (GC/EGJC): Data update from a phase II single-arm study

Background

Immunotherapy combined with trastuzumab and chemotherapy have been recommended by the clinical guidelines of many countries as the first-line treatment for advanced HER2-positive G/GEJC. Combining chemotherapy with tislizumab and trastuzumab in the neoadjuvant/adjuvant setting may benefit patients with locally advanced, resectable HER2-positive GC/GEJC.

Methods

This study is a multicenter, single-arm, open-label phase 2 study. Patients with histologically confirmed cT2-4NxM0 or cTxN+M0, resectable GC/GEJC were eligible for this study. Neoadjuvant therapy was administered for four cycles. The patients would receive tislelizumab and trastuzumab for 1 cycle (Q3W), followed by tislelizumab and trastuzumab combined with DOS (Docetaxel + Oxaliplatin + S-1) for 3 cycles (Q3W). Surgery was planned 4-6 weeks after preoperative treatment. Patients would receive adjuvant therapy starting within 4–6 weeks after surgery for 12 cycles. The primary endpoint is pathological complete response rate (pCR). Secondary endpoints include R0 resection rate, event-free survival (EFS), overall survival (OS) and safety.

Results

Between September 13, 2021 and April 30, 2024, 23 patients completed 4 cycles of neoadjuvant therapy (17 patients completed surgery, 4 patients requested organ preservation treatment after neoadjuvant therapy, 1 patient delayed surgery due to thyroid dysfunction, and 1 patient was inoperable due to progression). Median follow-up was 16.2 months. Among the surgery patients, R0 resection rate was 100%, 8 patients (47.1%) achieved pCR and 12 patients (70.6%) achieved MPR. pCR + cCR was 52.4% (11/21). Median OS and EFS were not yet reached in the surgical population, with 1-year OS and EFS rates of 91.7% and 83.3%. The most common AEs (grade ≥3) were neutropenia (13.0%) and anemia (8.7%). The immune-related adverse events were all grade 1. No treatment related death was reported.

Conclusions

According to the results, tislelizumab combined with trastuzumab and chemotherapy for the perioperative treatment of patients with HER2-positive GC and EGJ showed promising effect and a manageable safety profile.

Clinical trial identification

NCT04819971.

Editorial acknowledgement

Legal entity responsible for the study

The First Affiliated Hospital of Zhengzhou University.

Funding

BeiGene (Beijing) Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.