We aimed to investigate the efficacy and safety of S1 plus oxaliplatin in combination with tislelizumab, a novel engineered anti-PD-1 monoclonal antibody, and apatinib, an inhibitor of VEGFR-2, as neoadjuvant therapy for Borrmann IV、large Borrmann III type(tumor size>5cm) and Bulky N positive advanced gastric cancer (GC).
This was a single-arm, multicenter, open-label phase II trial (NCT05223088). Eligible patients (pts) had histologically proven advanced HER-2 negativeGC with Borrmann IV, large Borrmann III type(tumor size>5cm) and Bulky N positive. The surgery was performed after 4 cycles of drug treatment (S1+oxaliplatin+tislelizumab+apatinib).
Baseline Patient Characteristics: Among the 25 pts eligible which have been already postoperative efficacy evaluation in 40 pts, the median age was 57 years. The histological types were mainly poorly differentiated adenocarcinoma.
Characteristics N (%) Age, years Median 57 Mean 55.12±10.08 Range 39-73 Sex Male 19 (76.0) Female 6 (24.0) Enrollment factors Borrmann IV 3 (12.0) Borrmann III 20 (80.0) Bulky N positive 2 (8.0) Histological classification Moderately differentiated adenocarcinoma 2 (8.0) Poorly differentiated adenocarcinoma 23 (92.0) MSI status MSS 25 (100.0) MSI-H 0 (0.0) PD-L1（28-8）CPS score <1 5 (20.0) 1-5 13 (52.0) >5 7 (28.0) Tumor location Stomach 25 (80.0) Carcinoma of esophagogastric junction 5 (20.0) ECOG 0 7 (28.0) 1 18 (72.0)
Efficacy: Among the 25 pts eligible for preoperative efficacy evaluation, 23 achieved partial response (PR) and 2 had stable disease (SD), resulting in an overall response rate (ORR) of 92% and a disease control rate (DCR) of 100%. The rate of R0 resection was 100%. Six cases were diagnosed with pathological complete response (pCR). Nine cases were diagnosed with major pathologic response (MPR). The pCR rate (TRG 0) and MPR rate (TRG 0-1) were 24% and 36% respectively. The TRG 0-2 rate were 88%. Safety and tolerability: The incidence of adverse events (AEs) was 100%. The most common hematologic AEs were leukopenia (72.0%) and granulocytopenia (72.0%). The most common nonhematologic AEs included fatigue (80.0%) and cutaneous adverse reactions (28.0%).
Tislelizumab combined with apatinib and oxaliplatin plus S1 chemotherapy showed clinical benefits in Borrmann IV large Borrmann III type and Bulky N positive advanced GC, with acceptable safety profile.
NCT05223088.
The authors.
BeiGene.
All authors have declared no conflicts of interest.